Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Volume 77, Issue 1
Displaying 1-42 of 42 articles from this issue
Message From the Editor-in-Chief
Reviews
  • – Lessons Learned and Ongoing Challenges –
    Stephen J. Nicholls, Jordan Andrews, Rishi Puri, Kiyoko Uno, Yu Kataok ...
    2013 Volume 77 Issue 1 Pages 3-10
    Published: 2013
    Released on J-STAGE: December 25, 2012
    Advance online publication: November 25, 2012
    JOURNAL FREE ACCESS
    Advances in arterial wall imaging permit direct visualization of the full burden of atherosclerosis within the coronary arteries. When performed serially, these studies have demonstrated the importance of targeting major cardiovascular risk factors and provide an important opportunity for evaluation of novel therapies. The findings of these studies, the clinical implications and ongoing advances will be reviewed.  (Circ J 2013; 77: 3–10)
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  • Lin Chang, Hamblin Milton, Daniel T. Eitzman, Y. Eugene Chen
    2013 Volume 77 Issue 1 Pages 11-18
    Published: 2013
    Released on J-STAGE: December 25, 2012
    Advance online publication: December 01, 2012
    JOURNAL FREE ACCESS
    Perivascular adipose tissue (PVAT) is the fat tissue surrounding most of the vasculature and it has long been considered solely as vessel-supporting connective tissue. There are 2 major types of adipose tissue widely distributed throughout the body: white (WAT) and brown (BAT). PVAT is similar to BAT in rodents, but it was believed that only WAT existed in adult humans and BAT was present only in infants. However, the presence of functional BAT in adult humans is now accepted. The main function of BAT is to generate heat, and it is essential for adaptive thermogenesis and energy expenditure, whereas the main function of WAT is to store lipids. Besides the different functions of WAT and BAT, growing evidence suggests that different depots of adipose tissue have different functions. Similar to other fat depots, PVAT produces various adipokines, growth factors and inhibitors that affect functions of adjacent layers of the vasculature. Pathophysiological conditions such as obesity, vascular injury, aging and infection could cause PVAT dysfunction, leading to vascular endothelial and smooth muscle cell dysfunctions. In this review, we discuss the function and dysfunction of PVAT on atherosclerosis and hypertension.  (Circ J 2013; 77: 11–18)
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  • – Imaging, Techniques and Outcomes –
    Amar Krishnaswamy, Samir R. Kapadia, E. Murat Tuzcu
    2013 Volume 77 Issue 1 Pages 19-27
    Published: 2013
    Released on J-STAGE: December 25, 2012
    Advance online publication: December 15, 2012
    JOURNAL FREE ACCESS
    Paravalvular leak (PVL) is a known complication of surgical and transcatheter valve replacement procedures. Patients most commonly present with congestive heart failure and/or hemolysis, and repeat surgical procedures to correct the PVL carries increased risk with reduced likelihood of success. As a result, percutaneous approaches to PVL closure have been developed, with a considerable emphasis on multimodality imaging for both diagnosis and procedural guidance in the cardiac catheterization laboratory. Several large series of percutaneous PVL closure have been recently published, with encouraging results with respect to both procedural success and clinical outcomes. Here, we give a comprehensive review of imaging and procedural techniques for percutaneous PVL closure and present the data supporting this novel treatment strategy.  (Circ J 2013; 77: 19–27)
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  • Shinobu Itagaki, David H. Adams, Anelechi C. Anyanwu
    2013 Volume 77 Issue 1 Pages 28-34
    Published: 2013
    Released on J-STAGE: December 25, 2012
    Advance online publication: October 31, 2012
    JOURNAL FREE ACCESS
    Degenerative mitral valve disease is the most common etiology of mitral regurgitation in developed countries. Degenerative mitral valve disease should be distinguished from other valvular disease because most of the lesions caused by degenerative changes are amenable to valve repair as opposed to replacement, and successful durable repair with optimal timing can maintain the patient’s normal life expectancy. Despite dramatic surgical progress in degenerative mitral valve repair over the past few decades and detailing of surgical indications in established practice guidelines, prevailing data suggest a significant number of patients are still not referred for surgery in a timely fashion or are even denied for surgery for inappropriate reasons. This article reviews the current surgical triggers which all practicing cardiovascular specialists should be familiar with and which should prompt immediate surgical referral.  (Circ J 2013; 77: 28–34)
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2012 AHA Report
  • Jun Fujita
    2013 Volume 77 Issue 1 Pages 35-40
    Published: 2013
    Released on J-STAGE: December 25, 2012
    Advance online publication: December 12, 2012
    JOURNAL FREE ACCESS
    The American Heart Association (AHA) Scientific Sessions were held for the first time in Los Angeles in 2012, with the most up-to-date basic and clinical science in the field presented and heard by physicians, research scientists, students, and paramedical personnel from 100 countries. Japan accounted for the second highest number of submitted abstracts and the Japanese Circulation Society actively contributed to the success of the AHA Scientific Sessions this year. The Late-Breaking Clinical Trial sessions comprised 27 clinical studies presented in the main hall. The FREEDOM study revealed the superiority of using a coronary artery bypass graft for diabetic multivessel coronary artery diseases over percutaneous coronary intervention using a drug-eluting stent. A new peptide hormone, serelaxin, improved dyspnea in heart failure patients and significantly reduced mortality rates according to the RELAX-AHF study. In the basic sciences, primary necrosis in mitochondria was the hot topic, while genetics, including genome-wide association studies, and epigenetics were strong features of the basic and clinical cardiovascular (CV) science. It was also clear that regenerative medicine is now part of mainstream CV research, with several clinical trials underway and many basic research projects ongoing around the world. Induced pluripotent stem cells in particular have the potential to change CV medicine, and will underpin the next era of regenerative medicine and personal therapies for heart diseases.  (Circ J 2013; 77: 35–40)
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editorials
Original Articles
Arrhytmia/Electrophysiology
  • Hoyoun Won, Jong-Youn Kim, Jaemin Shim, Jae-Sun Uhm, Hui-Nam Pak, Moon ...
    2013 Volume 77 Issue 1 Pages 53-59
    Published: 2013
    Released on J-STAGE: December 25, 2012
    Advance online publication: September 22, 2012
    JOURNAL FREE ACCESS
    Background: The transient use of corticosteroid shortly after atrial fibrillation (AF) ablation might prevent immediate and mid-term AF recurrence; however, the effective dosage for preventing AF recurrence has not been determined. In this study, we evaluated whether low-dose hydrocortisone is effective for the prevention of AF recurrence after radiofrequency catheter ablation (RFCA). Methods and Results: We enrolled 89 AF patients (70 males, 55.8±10.9 years) who underwent RF ablation and were treated with single bolus injection of 100mg hydrocorticosteroid (corticosteroid group). For the control group, we enrolled 120 sex- and age-matched AF patients (94 males, 55.4±10.5 years). Pericarditis occurred in 3 (2.5%) and 1 (1.1%) patients in the control and corticosteroid groups, respectively. The number of patients with immediate AF recurrence (≤2 days) was 17 (14.5%) and 11 (12.4%) in the control and steroid groups, respectively (P=0.687). Treatment with low-dose steroid did not decrease early (3–30 days) AF recurrence (13 [11.1%] vs. 11 [12.5%], P=0.829) or late (≥31 days) AF recurrence after ablation (26 [22.2%] vs. 13 [14.6%], P=0.209). There was no difference in cumulative survival free of late AF recurrence between the corticosteroid and control groups (P=0.57 by log-rank test). White blood cell count, C-reactive protein concentration and maximum body temperature also were unchanged by low-dose steroid. Conclusions: Single bolus injection of low-dose hydrocortisone after AF ablation is not effective for preventing AF recurrence during the mid-term follow-up period.  (Circ J 2013; 77: 53–59)
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  • Tamiro Kawaguchi, Hideki Hayashi, Akashi Miyamoto, Tomohide Yoshino, A ...
    2013 Volume 77 Issue 1 Pages 60-67
    Published: 2013
    Released on J-STAGE: December 25, 2012
    Advance online publication: September 26, 2012
    JOURNAL FREE ACCESS
    Supplementary material
    Background: Progressive cardiac conduction disease (PCCD), characterized by temporal increase in PR interval and QRS duration, may be attributed to diverse pathophysiological mechanisms. This study aimed to investigate whether PCCD is associated with increased risk of cardiovascular morbidity and mortality. Methods and Results: Digital analysis of 12-lead ECG was performed to select patients with PCCD from among a database containing 359,737 ECGs. Long-term prognosis of PCCD was assessed in a large hospital-based population: 458 patients (341 males; mean age, 57.9±14.7 years) with PCCD were enrolled. During a mean follow-up of 13.3±6.4 years, 109 patients were hospitalized for heart failure (HF), and there were 16 and 59 deaths from cardiovascular diseases and all causes, respectively. Multivariate Cox proportional hazards analysis confirmed (1) a significant association of temporal incremental rate of PR interval (≥2ms/year) and QRS duration (≥3ms/year) with HF hospitalization (hazard ratio [HR], 2.34; 95% confidence interval [CI], 1.36–4.05; P=0.002 and HR, 2.08; 95% CI, 1.25–3.53; P=0.01, respectively) and (2) a significant association of temporal incremental rate of PR interval (≥4ms/year) and QRS duration (≥5ms/year) with cardiovascular mortality (HR, 6.9; 95% CI, 1.47–36.96; P=0.02 and HR, 4.31; 95% CI, 1.19–16.5; P=0.03, respectively). Conclusions: The severity of PCCD was independently and significantly associated with HF hospitalization and cardiovascular mortality.  (Circ J 2013; 77: 60–67)
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  • – A Transesophageal Echocardiography Study –
    Hiroyuki Okura, Toru Kataoka, Minoru Yoshiyama, Junichi Yoshikawa, Kiy ...
    2013 Volume 77 Issue 1 Pages 68-72
    Published: 2013
    Released on J-STAGE: December 25, 2012
    Advance online publication: October 06, 2012
    JOURNAL FREE ACCESS
    Background: Both left atrial spontaneous echo contrast (LASEC) and aortic atherosclerotic plaque (AoP) ≥4.0mm in thickness are predictors of cardiovascular events after stroke. The aim of this study was to investigate impact of AoP ≥4.0mm or LASEC on cardiovascular events in patients with atrial fibrillation (AF). Methods and Results: One hundred and eight consecutive patients with AF were enrolled and studied. Patients were grouped according to the presence or absence of AoP ≥4.0mm in the proximal aortic arch on transesophageal echocardiography (TEE). Cardiovascular events included death, myocardial infarction, ischemic stroke, systemic embolism and congestive heart failure. During a follow-up period (median, 3.9 years), cardiovascular event-free survival rate was significantly lower in patients with AoP ≥4.0mm than in patients without AoP ≥4.0mm (log-rank, P=0.01). In contrast, patients with LASEC showed a trend toward lower cardiovascular event-free survival than those without LASEC (log-rank, P=0.10). Univariate TEE predictors of cardiovascular events were AoP ≥4.0mm, LASEC and left atrial appendage flow velocity. On multivariate Cox regression analysis, AoP ≥4.0mm was the only TEE predictor of cardiovascular events during follow-up (P=0.02, hazard ratio, 2.6; 95% confidence interval: 1.1–6.0). Conclusions: In the present unselected patients with AF, AoP predicted long-term cardiovascular events.  (Circ J 2013; 77: 68–72)
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Cardiovascular Intervention
  • – Insights From In Vitro Experiments and Micro-Computed Tomography –
    Nicolas Foin, Eduardo Alegria-Barrero, Ryo Torii, Pak H. Chan, N. Vice ...
    2013 Volume 77 Issue 1 Pages 73-80
    Published: 2013
    Released on J-STAGE: December 25, 2012
    Advance online publication: September 25, 2012
    JOURNAL FREE ACCESS
    Background: Percutaneous coronary intervention of complex true bifurcation lesions often fails to ensure continuous stent coverage and strut apposition in both the side branch and main vessel. Struts left unopposed floating in the lumen disturb blood flow and are increasingly recognized as increasing the risk of stent thrombosis. Methods and Results: In this study, we compared the results of different bifurcation treatment strategies: Crush (n=5); Culotte (n=3); T-/T with Protrusion (TAP) (n=4) using drug-eluting stents deployed in-vitro in representative coronary bifurcation models. After final kissing balloon post-dilatation, the rate of malapposition within the bifurcation quantified from micro-computed tomography scanning was on average 41.5±8.2% with the Crush technique, reduced to respectively 31.4±5.2% with Culotte and 36.7±8.0% with T-/TAP approach. Overlaying layers of struts in the Crush and Culotte techniques lead to a significantly higher rate of strut malapposition in the proximal vessel than with the T-/TAP technique (Crush: 39.1±10.7%, Culotte: 26.1±7.7%, TAP: 4.2±7.2%, P<0.01). Maximal wall-malapposed strut distance was also found on average to be higher with the Crush (1.36±0.4mm) and Culotte techniques (1.32±0.1mm) than with T-/TAP (1.08±0.1mm, P=0.04). Conclusions: In this model, the Crush technique resulted in a higher risk of malapposition than either the Culotte or T-/TAP technique.  (Circ J 2013; 77: 73–80)
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  • – Five-Year Cardiac Magnetic Resonance Imaging Follow-up –
    Tirza Springeling, Sharon W. Kirschbaum, Alexia Rossi, Timo Baks, Yusu ...
    2013 Volume 77 Issue 1 Pages 81-88
    Published: 2013
    Released on J-STAGE: December 25, 2012
    Advance online publication: September 27, 2012
    JOURNAL FREE ACCESS
    Background: Primary percutaneous coronary intervention (PPCI) preserves function and improves survival. The late effects of PPCI on left ventricular remodeling, however, have not yet been investigated on cardiac magnetic resonance imaging (CMRI). Methods and Results: Twenty-five patients with acute myocardial infarction (AMI) treated with PPCI underwent CMRI within 10 days, at 4 months and at 5 years. Left ventricular ejection fraction (LVEF), end-diastolic volume (EDV) and end-systolic volume were quantified on cine images. Infarct mass and transmural extent of infarction were quantified on contrast-enhanced imaging. In all patients EDV increased significantly in the early phase (192±40ml to 211±49ml, P≤0.01) and LVEF improved significantly (42±9% to 46±9%, P=0.02). In the late phase (>4 months) no significant changes were observed (LVEF 44±9%, P=0.07; EDV 216±68ml, P=0.38). Three different groups could be identified. One-third (32%) had no dilatation at all; one-third (32%) had limited dilatation at 4 months without progression later; and 36% had progressive dilatation both at 4 months and at late follow-up. This third group had an average increase in EDV of 20% in the acute phase followed by an additional 13%. The strongest predictor for progressive dilatation was infarct mass. Conclusions: Even in the era of PPCI for AMI followed by optimal medical therapy, one-third of patients had progressive dilatation, which was best predicted by infarct mass.  (Circ J 2013; 77: 81–88)
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  • Takashi Miura, Yoshimitsu Soga, Tatsuki Doijiri, Hideaki Aihara, Hiroy ...
    2013 Volume 77 Issue 1 Pages 89-95
    Published: 2013
    Released on J-STAGE: December 25, 2012
    Advance online publication: September 26, 2012
    JOURNAL FREE ACCESS
    Background: The goal of this study was to evaluate the prevalence and outcomes of polyvascular disease (polyVD; defined as lower extremity artery disease, carotid artery disease, renal artery disease, or abdominal aortic aneurysm) in patients undergoing percutaneous coronary intervention (PCI). Methods and Results: The subjects were 1,597 patients who underwent PCI and who were prospectively enrolled in the study. The carotid, renal and peripheral arteries and abdominal aorta were simultaneously evaluated using duplex ultrasound and ankle-brachial index to evaluate the presence of polyVD. The primary endpoint was major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction [MI], and stroke). PolyVD was found in 446 of 1,597 patients (27.9%). MACE were significantly higher in the polyVD group compared to those with coronary artery disease (CAD) alone (n=1,151; 12.1% vs. 3.8%, P<0.0001). The incidence of cardiovascular death and stroke were significantly higher in the polyVD group (7.9% vs. 1.6%, P<0.0001; 3.6% vs. 1.2%, P=0.006, respectively). The incidence of MI was similar in the 2 groups (3.7% vs. 1.3%, P=0.08). The adjusted hazard ratios for MACE in patients with 1, 2, and 3 arterial beds (compared with CAD alone) increased from 1.64 to 1.74 to 10.62 (P<0.0001). Conclusions: There was a high incidence of MACE in patients with polyVD undergoing PCI and this incidence increased with the number of arterial beds.  (Circ J 2013; 77: 89–95)
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Cardiovascular Surgery
  • Teruhiko Imamura, Koichiro Kinugawa, Taro Shiga, Miyoko Endo, Naoko Ka ...
    2013 Volume 77 Issue 1 Pages 96-104
    Published: 2013
    Released on J-STAGE: December 25, 2012
    Advance online publication: September 11, 2012
    JOURNAL FREE ACCESS
    Background: It is often difficult to predict reversibility of liver or renal function after left ventricular assist device (LVAD) implantation in patients with stage D heart failure. Methods and Results: Data were obtained for 69 patients who had received a LVAD (18 continuous-flow, 51 pulsatile). Persistent hepatic or renal dysfunction was defined as levels of total bilirubin (TB) or creatinine (Cre) >1.5mg/dl at 6 months after LVAD implantation. TB score or Cre score was calculated: 0.15×age+1.1× (preoperative TB) or 0.2×age+3.6× (preoperative Cre), in which coefficients were determined on the basis of odds ratios for persistent hepatic or renal dysfunction, respectively. Receiver-operating characteristics analyses showed good predictabilities for persistent end-organ dysfunction (area under curve: 0.794 for TB score and 0.839 for Cre score). High-risk strata of TB score (>11.0 points) or Cre score (>14.1 points) were associated with persistently higher levels of TB or Cre (TB, 1.32±0.51; Cre, 1.23±0.41mg/dl; both P<0.001 vs. low-risk strata). Conclusions: Reversibility of end-organ function with LVAD implantation can be well predicted by our new risk scoring system that consists of the preoperative TB or Cre level adjusted by the patient’s age. The scoring system would be beneficial, especially in considering the indication of a bridge to candidacy.  (Circ J 2013; 77: 96–104)
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  • Shigeaki Aoyagi, Kei-ichiro Tayama, Teiji Okazaki, Yusuke Shintani, Mi ...
    2013 Volume 77 Issue 1 Pages 105-108
    Published: 2013
    Released on J-STAGE: December 25, 2012
    Advance online publication: September 21, 2012
    JOURNAL FREE ACCESS
    Background: The durability of the Starr-Edwards (SE) mitral caged-disk valve, model 6520, is not clearly known, and structural valve deterioration in the SE disk valve is very rare. Methods and Results: Replacement of the SE mitral disk valve was performed in 7 patients 23–40 years after implantation. Macroscopic examination of the removed disk valves showed no structural abnormalities in 3 patients, in whom the disk valves were removed at <26 years after implantation. Localized disk wear was found at the sites where the disk abutted the struts of the cage, in disk valves excised >36 years after implantation in 4 patients. Disk fracture, a longitudinal split in the disk along its circumference at the site of incorporation of the titanium ring, was detected in the valves removed 36 and 40 years after implantation, respectively, and many cracks were also observed on the outflow aspect of the disk removed 40 years after implantation. Conclusions: Disk fracture and localized disk wear were found in the SE mitral disk valves implanted >36 years previously. The present results suggest that SE mitral caged-disk valves implanted >20 years previously should be carefully followed up, and that those implanted >30 years previously should be electively replaced with modern prosthetic valves.  (Circ J 2013; 77: 105–108)
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  • Jin Wi, Jae-Young Choi, Jae-Min Shim, Jae-Sun Uhm, Hye-Jin Hwang, Jong ...
    2013 Volume 77 Issue 1 Pages 109-115
    Published: 2013
    Released on J-STAGE: December 25, 2012
    Advance online publication: October 16, 2012
    JOURNAL FREE ACCESS
    Background: Atrial fibrillation (AF) is common among adult patients with an atrial septal defect (ASD). Catheter ablation or the Maze procedure can be considered for AF before or concurrently with ASD closure. However, the fate of preoperative AF is not well established. This study examined the postoperative course of patients with AF before undergoing ASD correction. Methods and Results: The 471 patients (131 men, 42±14 years) underwent transcatheter closure (n=237, 50%) or surgical repair (n=234, 50%) of an ASD. ECG and Holter monitoring were used to document preoperative and postoperative AF. Forty patients had AF before transcatheter closure (n=10) or surgical repair (n=30) of the ASD. During the follow-up period of 44±28 months, excluding 15 patients who had undergone surgical repair with the Maze procedure, sinus rhythm (SR) was maintained in 7 (88%) of 8 patients with paroxysmal AF. However, only 3 (18%) of 17 patients with persistent AF maintained SR. Among the 15 patients treated with the Maze procedure, 12 (80%) maintained SR. Conclusions: Hemodynamic correction of ASD was effective in conversion to SR in most patients with preoperative paroxysmal AF. However, the Maze procedure or transcatheter ablation before ASD correction needs to be considered for the treatment of AF in patients with persistent AF.  (Circ J 2013; 77: 109–115)
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Heart Failure
  • Kenshiro Arao, Takayuki Fujiwara, Kenichi Sakakura, Hiroshi Wada, Yosh ...
    2013 Volume 77 Issue 1 Pages 116-122
    Published: 2013
    Released on J-STAGE: December 25, 2012
    Advance online publication: September 28, 2012
    JOURNAL FREE ACCESS
    Background: Various factors associated with worsening heart failure (HF) events have been investigated in HF subjects. The purpose of this study was to identify the predictive factor(s) for worsening HF events after cardiac resynchronization therapy (CRT) among baseline parameters, as well as baseline factors associated with responsiveness or non-responsiveness to CRT. Methods and Results: Seventy-seven HF patients with an indication for CRT were enrolled. Baseline parameters of blood chemistry, electrocardiogram, echocardiogram and cardiac catheterization before device implantation were measured, and subsequent clinical HF events after CRT were investigated. During the follow-up period (median 601 days), 22 of 77 (29%) recipients had HF events (unscheduled HF hospitalization: 16; use of left ventricular assist system: 1; heart transplantation: 1; cardiac death: 4). In the multivariate Cox proportional hazards model, low serum sodium concentration was associated with the occurrence of HF events after CRT (hazard ratio 0.82, 95% confidence interval 0.68–0.99, P=0.034). At baseline, serum sodium concentration negatively correlated with pulmonary capillary wedge pressure (r=−0.71, P<0.001) and with plasma arginine vasopressin level (r=−0.68, P=0.008). Conclusions: Hyponatremia is an independent predictor for worsening HF events after CRT implantation, which may be partly explained by elevated level of plasma arginine vasopressin.  (Circ J 2013; 77: 116–122)
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  • Toshihiko Goto, Nobuyuki Ohte, Hidekatsu Fukuta, Kazuaki Wakami, Tomom ...
    2013 Volume 77 Issue 1 Pages 123-129
    Published: 2013
    Released on J-STAGE: December 25, 2012
    Advance online publication: September 29, 2012
    JOURNAL FREE ACCESS
    Background: Heart failure with preserved ejection fraction (HFpEF) is frequently observed in older women. Increased arterial stiffness in this population may be a cause of HFpEF. Methods and Results: In 75 patients who underwent cardiac catheterization and who had no significant coronary artery stenosis or left ventricular (LV) wall motion abnormalities, the LV relaxation time constant (Tp) was calculated. The LVEF was obtained from left ventriculography, and plasma brain natriuretic peptide (BNP) level was measured. From the pressure waveforms at the ascending aorta, the augmentation index (AIx) was calculated. Effective arterial elastance (Ea) and total vascular resistance (TVR) were also determined. No significant differences were found between genders for age, heart rate, central blood pressure, or LVEF. Ea, TVR, AIx, and BNP level were significantly greater in women than in men, but only AIx was significantly correlated with Tp (r=0.25, P=0.04) and BNP level (r=0.33, P=0.005). Conclusions: The arterial system is stiffer in women than in men of the same age. Among the parameters of arterial stiffness, only AIx is related to abnormal LV relaxation and increased BNP level. Elevated AIx is a factor that causes LV diastolic dysfunction and may be associated with the development of HFpEF in this gender.  (Circ J 2013; 77: 123–129)
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Hypertension and Circulatory Control
  • Yukichi Murozono, Kunio Yufu, Naohiko Takahashi, Norihiro Okada, Tetsu ...
    2013 Volume 77 Issue 1 Pages 130-136
    Published: 2013
    Released on J-STAGE: December 25, 2012
    Advance online publication: September 27, 2012
    JOURNAL FREE ACCESS
    Background: We previously reported that baroreflex sensitivity (BRS) or cardiac iodine 123 metaiodobenzylguanidine (123I-MIBG) scintigraphic findings can predict cardiovascular prognosis in type 2 diabetic patients. We therefore tested the hypothesis that the combination of BRS and 123I-MIBG scintigraphic findings could strengthen the predictive power for major adverse cerebral and cardiovascular events (MACCE). Methods and Results: From 1998, we have evaluated both BRS and 123I-MIBG scintigraphy in 165 type 2 diabetic patients (77 females, 88 males, mean age 59±12 years). Based on the ROC curves, depressed BRS was defined as <5.63mmHg/s, and enhanced washout ratio (WR) was defined as ≥41.4%. Each patient was divided into 3 groups based on the “BRS-MIBG combination score” as follows: 0, patients having both preserved BRS and preserved WR; 1, patients having either depressed BRS or enhanced WR; 2, patients having both depressed BRS and enhanced WR. During the mean of 4.7±2.7 years of follow-up, 19 patients developed MACCE. The MACCE-free ratio was significantly higher in the lower BRS-MIBG combination score group (log-rank 16.41, P=0.0003). Cox proportional hazards regression analysis revealed that BRS-MIBG combination score was independently associated with the incidence of MACCE (hazard ratio 4.06, P=0.0237). Conclusions: Our results suggest that combined assessment of the BRS and 123I-MIBG scintigraphic findings is more useful for identifying the type 2 diabetic patients at high risk for MACCE.  (Circ J 2013; 77: 130–136)
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Imaging
  • Ryota Fukuoka, Yuki Horita, Masanobu Namura, Masatoshi Ikeda, Hidenobu ...
    2013 Volume 77 Issue 1 Pages 137-145
    Published: 2013
    Released on J-STAGE: December 25, 2012
    Advance online publication: October 03, 2012
    JOURNAL FREE ACCESS
    Background:18F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) is assumed to be the most useful method for evaluating the viability of the myocardium. However, there are few reports regarding serial changes in 18F-FDG-PET images of acute myocardial infarction (AMI). We evaluated serial changes in glucose-loaded 18F-FDG-PET, 123I-β-methyl-p-iodophenyl-penta-decanoic acid (BMIPP) single-photon emission computed tomography (SPECT) and 99mTc-Tetrofosmin (TF) gated SPECT images in patients with AMI. Methods and Results: We enrolled 7 consecutive patients with first anterior AMI who successfully underwent percutaneous coronary intervention (PCI). 18F-FDG-PET images were obtained in the acute, subacute, chronic, mid-term and long-term phases. 123I-BMIPP and 99mTc-TF SPECT images were obtained in the subacute, chronic, mid-term and long-term phases. We determined the total defect score (TDS) for each image. The TDS of the glucose-loaded 18F-FDG-PET, 123I-BMIPP and 99mTc-TF SPECT images indicated significant serial decrease (P<0.001). Comparing these images, the TDS of the glucose-loaded 18F-FDG-PET images was larger than that of the 123I-BMIPP and 99mTc-TF SPECT images, and the TDS indicated 18F-FDG-PET>123I-BMIPP>99mTc-TF in all phases. Conclusions: The defect areas of glucose-loaded 18F-FDG-PET images were significantly larger than those of 123I-BMIPP and 99mTc-TF SPECT images during 9 months follow-up of patients with successful PCI for anterior AMI. Additionally, the impairment of glucose metabolism was prolonged.  (Circ J 2013; 77: 137–145)
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  • Kazuhiro Osawa, Toru Miyoshi, Shuhei Sato, Noriaki Akagi, Yusuke Morim ...
    2013 Volume 77 Issue 1 Pages 146-152
    Published: 2013
    Released on J-STAGE: December 25, 2012
    Advance online publication: October 03, 2012
    JOURNAL FREE ACCESS
    Background: We evaluated the safety and efficacy of a bolus injection of landiolol hydrochloride, an ultrashort-acting β1-selective antagonist, as an additional treatment after premedication with an oral β-blocker to reduce heart rate prior to multidetector-row computed tomography (MDCT) coronary angiography (CAG). Methods and Results: A total of 458 patients who underwent MDCT CAG were retrospectively enrolled. Image quality and hemodynamic parameters were compared in patients before and after approval of landiolol hydrochloride. If heart rate reduction was insufficient after premedication with an oral β-blocker, a bolus injection of landiolol hydrochloride (n=66) or other drugs (n=30) was used. The percentage of evaluable images per segment in patients after approval of landiolol (99.3%) was greater than that in patients before approval of landiolol (97.4%, P<0.01). Heart rates before scanning in patients receiving landiolol hydrochloride were similar to those receiving other drugs. Heart rate was significantly reduced approximately 5min after injection of landiolol hydrochloride and increased shortly. No decrease in systolic blood pressure or other adverse effects was observed. Conclusions: Bolus injection of landiolol hydrochloride sufficiently reduced heart rate without significantly reducing systolic blood pressure and produced a high percentage of evaluable images, suggesting that bolus injection of landiolol hydrochloride as an additional pretreatment is feasible in MDCT CAG.  (Circ J 2013; 77: 146–152)
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Ischemic Heart Disease
  • Masahiko Hara, Yasuhiko Sakata, Daisaku Nakatani, Shinichiro Suna, Mas ...
    2013 Volume 77 Issue 1 Pages 153-162
    Published: 2013
    Released on J-STAGE: December 25, 2012
    Advance online publication: October 06, 2012
    JOURNAL FREE ACCESS
    Supplementary material
    Background: Intake of long-chain n-3 polyunsaturated fatty acids (n-3 PUFA), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), is associated with a lower risk of atherosclerotic cardiovascular events, particularly acute myocardial infarction (AMI). However, limited data are available regarding the association between serum n-3 PUFA levels and heart failure (HF) events in survivors of AMI. Methods and Results: We evaluated whether serum DHA and EPA levels were associated with HF-free survival and HF hospitalization rates after AMI. A total of 712 patients were divided into 3 groups according to their tertile serum levels of DHA and EPA (Low, Middle, and High). Propensity-score-stratified Cox regression analysis revealed that DHA- and EPA-Low groups presented statistically significant worse HF-free survival (hazard ratio (HR) 1.68, 95% confidence interval (CI) 1.03–2.72, P=0.0358, and HR 1.69, 95% CI 1.05–2.72, P=0.0280, respectively), with the EPA-Low group having a higher risk of HF hospitalization (HR 2.40, 95% CI 1.21–4.75, P=0.0097) than the DHA-Low group (HR 1.72, 95% CI 0.86–3.45, P=0.1224). The relationship between a low DHA or EPA level and decreased HF-free survival was almost common to all subgroups; however, the effect of low serum EPA on HF hospitalization was prominent in male patients, and those with low levels of high-density lipoprotein cholesterol or without statin therapy. Conclusions: Low levels of circulating n-3 PUFA are associated with decreased HF-free survival in post-AMI patients.  (Circ J 2013; 77: 153–162)
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Metabolic Disorder
  • Ioannis Skoumas, Constantina Masoura, Konstantinos Aznaouridis, Vassil ...
    2013 Volume 77 Issue 1 Pages 163-168
    Published: 2013
    Released on J-STAGE: December 25, 2012
    Advance online publication: September 28, 2012
    JOURNAL FREE ACCESS
    Background: Familial combined hyperlipidemia (FCH) is an inherited lipid disorder associated with premature cardiovascular disease. It has not been established whether the cardiometabolic risk factors, which frequently accompany FCH, such as diabetes, metabolic syndrome (MetS) and hypertension, modulate cardiovascular risk in FCH patients. Methods and Results: In this single-center, retrospective study, 695 FCH patients with adequate follow-up were enrolled (mean age, 48.9 years; 455 male). Risk factors including lipid levels were evaluated before the initiation of treatment. Acute myocardial infarction (AMI) and cardiovascular death were recorded during a mean follow-up of 9 years. The combined endpoint (AMI and/or cardiovascular death) occurred in 41 patients (5.9% of the total). Those FCH patients who reached the combined endpoint had lower high-density lipoprotein cholesterol (HDL-C) than those who did not, but levels of other lipid variables were similar. Presence of hypertension, diabetes or MetS was a predictor of the combined endpoint on univariate Kaplan-Meier analysis (all P<0.005). Multivariate Cox proportional analysis showed that hypertension and MetS were associated with the combined endpoint independently of age, gender, HDL-C and presence of coronary artery disease at enrolment (adjusted hazard ratios [HRs], 3.00; 95% confidence interval [CI]: 1.46–6.17, P=0.003; HR, 2.43; 95CI%: 1.11–5.33, P=0.026, respectively). Conclusions: Cardiometabolic risk factors such as hypertension and MetS are independent predictors of major cardiovascular events in FCH patients.  (Circ J 2013; 77: 163–168)
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Molecular Cardiology
  • – Family-Based Association Study –
    Fuqiang Liu, Shuhui Zheng, Jianjun Mu, Chao Chu, Lan Wang, Yang Wang, ...
    2013 Volume 77 Issue 1 Pages 169-174
    Published: 2013
    Released on J-STAGE: December 25, 2012
    Advance online publication: October 12, 2012
    JOURNAL FREE ACCESS
    Background: Common variations in the gene with no-lysine kinase 1 (WNK1) are associated with hypertension, but because of gene-environment interaction, it is difficult to fully identify the genetic contribution of WNK1 gene polymorphism to blood pressure (BP) variability. The aim of this study was to identify the effect of common WNK1 variants on the shift of BP during strict dietary interventions of salt or potassium intake. Methods and Results: A total of 342 subjects from 126 families were selected and sequentially maintained on normal diet for 3 days at baseline, a low-salt diet for 7 days (3g/day, NaCl), then a high-salt diet for 7 days (18g/day), and high-salt diet with potassium supplementation for another 7 days (4.5g/day, KCl). Five single nucleotide polymorphisms (SNPs) were selected from the WNK1 gene. rs880054 and rs12828016 were associated with diastolic BP (DBP) response during the low-or high-sodium intervention, and rs2301880 was significantly associated with systolic BP, DBP and mean arterial pressure responses to the high-sodium intervention (all P<0.05). Unfortunately, no associations for WNK1 SNPs and the constructed haplotype blocks of WNK1 with BP responses to high-salt-and-potassium supplement intervention reached nominal statistical significance. Conclusions: The WNK1 gene might be mechanistically involved in the variation in BP response to dietary sodium and potassium intake among individuals, and might contribute to the variation of this complex phenotype.  (Circ J 2013; 77: 169–174)
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Myocardial Disease
  • – New Physiopathological Hypothesis –
    Clément Delmas, Olivier Lairez, Emmanuel Mulin, Thomas Delmas, ...
    2013 Volume 77 Issue 1 Pages 175-180
    Published: 2013
    Released on J-STAGE: December 25, 2012
    Advance online publication: September 13, 2012
    JOURNAL FREE ACCESS
    Background: Recent retrospective studies suggest that psychiatric disorders could be a predisposing risk factor for Tako-tsubo cardiomyopathy (TTC). The aim of the present study was to characterize the prevalence of anxiodepressive disorders (ADD) and chronic psychological stress (CPS) in patients with TTC or acute coronary syndrome (ACS). Methods and Results: Between January 2010 and December 2011, 45 consecutive patients with TTC were prospectively screened by systematic interview with the Mini International Neuropsychiatric Interview. CPS was systematically recorded. During the same period, 50 patients admitted for ACS with troponin elevation and matched for age and sex were prospectively included as a control group. An acute stressful event within 72h before presentation was identified in 35 patients (78%) with TTC vs. 9 (18%) with ACS (P<0.001). Thirty-five patients (78%) and 13 (26%) had ADD in the TTC and ACS groups, respectively (P<0.001). CPS was found in 20 patients (44%) and in 9 (18%) with TTC and ACS, respectively (P=0.005). CPS and/or ADD were found in 35 patients (78%) and in 18 (36%) with TTC and ACS, respectively (P<0.001). Conclusions: ADD and CPS are common in patients with TTC and more frequent than in patients with ACS. This finding suggests that systemic effects of ADD and CPS could participate in the pathophysiology of TTC.  (Circ J 2013; 77: 175–180)
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Pediatric Cardiology and Adult Congenital Heart Disease
  • Ying-Jui Lin, Chien-Ning Hsu, Mao-Hung Lo, Chien-Fu Huang, Shao-Ju Chi ...
    2013 Volume 77 Issue 1 Pages 181-187
    Published: 2013
    Released on J-STAGE: December 25, 2012
    Advance online publication: September 20, 2012
    JOURNAL FREE ACCESS
    Background: Nitric oxide (NO) is involved in hypertension and chronic kidney disease (CKD). NO synthase can metabolize L-arginine (ARG) to generate NO and L-citrulline (CIT). Two methylated ARG derivatives, asymmetric and symmetric dimethylarginine, are also involved in NO deficiency. Thus it was hypothesized that their combined ratios relate to blood pressure (BP) abnormalities in children with early CKD. Methods and Results: The relationship between these ARG metabolites in plasma was examined using 24-h ambulatory BP monitoring (ABPM) profile in children and adolescents with CKD stages 1–3 (n=44). Approximately 20.4% (9/44) of children with CKD stages 1–3 were diagnosed with hypertension on clinical BP measurement, and 77.3% (33/44) had BP abnormalities on ABPM, including increased BP load, nocturnal BP non-dipping, and nocturnal hypertension. Children with CKD stages 2–3 were more prevalent with abnormal BP on ABPM, and had a higher level of CIT and CIT-to-ARG ratio than those with stage 1. Furthermore, high CIT-to-ARG ratio was significantly correlated with abnormal ABPM profile, including nocturnal hypertension, increased diastolic BP load, and nocturnal BP non-dipping. Higher CIT level was significantly correlated with increased diastolic BP load and overall ABPM profile. Conclusions: Plasma CIT-to-ARG ratio may serve as a useful marker of cardiovascular outcome in children with early CKD.  (Circ J 2013; 77: 181–187)
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  • – Age-Related Variations and Prognostic Value –
    Massimiliano Cantinotti, Valentina Lorenzoni, Simona Storti, Riccardo ...
    2013 Volume 77 Issue 1 Pages 188-197
    Published: 2013
    Released on J-STAGE: December 25, 2012
    Advance online publication: September 27, 2012
    JOURNAL FREE ACCESS
    Background: Interest in hormonal response after pediatric cardiac surgery is growing, but many aspects remain unclear. The aim of this study was to test age-related variations and prognostic values of thyroid hormones, and brain natriuretic peptide (BNP) levels before and after surgery. Methods and Results: A total of 162 children undergoing cardiac surgery were divided into 3 age groups (group 1, n=57 neonates; group 2, n=58 infants; group 3, n=47 toddlers). Free thyroid hormones (fT3 and fT4), thyrotropin (thyroid-stimulating hormone [TSH]) and BNP were measured preoperatively, daily postoperatively in the intensive care unit and after 15 days. The primary outcome was time to extubation (TTE; variable used as time to event by survival analysis). The hormonal response differed among age groups. In older children the TSH nadir occurred at 6–12h after surgery (0.42mIU/L, P<0.001), with a progressive recovery thereafter, while in neonates the TSH nadir occurred later, at 36–60h (0.14mIU/L, P<0.001), followed by a much slower recovery. In neonates, BNP also dropped after surgery (from 2,899 to 824.0ng/L, P<0.001) while increased in older children (from 71.00 to 527.00ng/L, P<0.001). On multivariate analysis independent predictors of TTE were fT3 nadir in all age groups, together with TSH nadir and Aristotle score in neonates, and body surface area and BNP peak in older children. Conclusions: BNP and thyroid response after pediatric cardiac surgery differs widely according to age. Beside Aristotle score, combined measurement of fT3 and TSH are the strongest predictors of TTE, especially in neonates.  (Circ J 2013; 77: 188–197)
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Pulmonary Circulation
  • Toshiro Inaba, Atsushi Yao, Tomoko Nakao, Masaru Hatano, Hisataka Maki ...
    2013 Volume 77 Issue 1 Pages 198-206
    Published: 2013
    Released on J-STAGE: December 25, 2012
    Advance online publication: September 28, 2012
    JOURNAL FREE ACCESS
    Background: Non-invasive assessment of volume and function on the right ventricle (RV) for pulmonary hypertension (PH) is limited. Methods and Results: Patients with PH (n=23) underwent 3-dimensional (D) echocardiography (3DECHO), with cardiac magnetic resonance imaging to confirm its precision, and right heart catheterization. On linear regression analysis the RV end-systolic volume index (ESVI) was positively correlated with pulmonary vascular resistance (PVR) and mean pulmonary arterial pressure (mPAP; R=0.42 and 0.46, P=0.03 and 0.03, respectively). The RV end-diastolic volume index (EDVI) was positively correlated with mPAP (R=0.41, P<0.05). The left ventricular (LV) EDVI was inversely correlated with PVR (R=−0.48, P=0.02). The RV ejection fraction was inversely correlated with PVR and mean right atrial pressure (mRAP; R=−0.57, and −0.45, P=0.004, and 0.03, respectively). RVEDVI/LVEDVI and RVESVI/LVESVI (the diastolic and systolic remodeling indices, respectively) had a significantly positive linear relationship with PVR (R=0.67 and 0.55, P=0.0005 and 0.006, respectively), and the former had a significantly positive linear relationship with mRAP (R=0.42, P<0.05). During the recovery process in 1 specific case, the remodeling indices maintained a significant linear relationship with the hemodynamic parameters. Conclusions: Novel indices provided by 3DECHO may be utilized as alternative indicators of hemodynamic changes in PH patients.  (Circ J 2013; 77: 198–206)
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Regenerative Medicine
  • Alexander Weymann, Bastian Schmack, Takayuki Okada, Pál So&oacu ...
    2013 Volume 77 Issue 1 Pages 207-216
    Published: 2013
    Released on J-STAGE: December 25, 2012
    Advance online publication: September 21, 2012
    JOURNAL FREE ACCESS
    Supplementary material
    Background: Heart valve tissue engineering represents a concept for improving the current methods of valvular heart disease therapy. The aim of this study was to develop tissue engineered heart valves combining human umbilical vein endothelial cells (HUVECs) and decellularized human heart valve matrices. Methods and Results: Pulmonary (n=9) and aortic (n=6) human allografts were harvested from explanted hearts from heart transplant recipients and were decellularized using a detergent-based cell extraction method. Analysis of decellularization success was performed with light microscopy, transmission electron microscopy and quantitative analysis of collagen and elastin content. The decellularization method resulted in full removal of native cells while the mechanical stability and the quantitative composition of the neoscaffolds was maintained. The luminal surface of the human matrix could be successfully recellularized with in vitro expanded HUVECs under dynamic flow conditions. The surface appeared as a confluent cell monolayer of positively labeled cells for von Willebrand factor and CD 31, indicating their endothelial nature. Conclusions: Human heart valves can be decellularized by the described method. Recellularization of the human matrix resulted in the formation of a confluent HUVEC monolayer. The in vitro construction of tissue-engineered heart valves based on decellularized human matrices followed by endothelialization using HUVECs is a feasible and safe method, leading to the development of future clinical strategies in the treatment of heart valve disease.  (Circ J 2013; 77: 207–216)
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Renal Disease
  • Ming-Jer Hsieh, Yung-Chang Chen, Chun-Chi Chen, Chun-Li Wang, Lung-She ...
    2013 Volume 77 Issue 1 Pages 217-223
    Published: 2013
    Released on J-STAGE: December 25, 2012
    Advance online publication: September 13, 2012
    JOURNAL FREE ACCESS
    Background: Recent studies have proven that initial renal dysfunction and worsening renal function during hospitalization can predict the clinical outcome of patients with acute myocardial infarction (AMI). There is limited study regarding acute kidney injury (AKI) by the RIFLE classification (Risk of renal failure, Injury to the kidney, Failure of kidney function, Loss of kidney function, and End-stage renal failure) to assess the outcome of AMI survivors. Methods and Results: During a mean follow-up period of 635.3±204.9 days, the 2-year mortality rate was 10.6% in 613 AMI patients who survived to discharge. Adjusted Cox regression analysis revealed that left ventricular dysfunction (<40%) [hazard ratio (HR), 2.83; 95% confidence interval (CI), 1.11–7.20; P=0.029], estimated glomerular filtration rate <60ml·min–1·1.73m−2 on admission (HR, 4.01; 95% CI, 1.51–10.62; P=0.005), and AKI severity by RIFLE classification during first week after hospitalization (Injury: HR, 8.11; 95% CI, 2.53–26.05; P=0.001; Failure: HR, 19.28; 95% CI, 2.24–166.26; P=0.007) were independent predictors of 2-year mortality. Conclusions: Independent of initial renal dysfunction on admission, the AKI severity by RIFLE classification may be useful in establishing the hospital discharge risk score for predicting long-term mortality in AMI patients who survive to discharge.  (Circ J 2013; 77: 217–223)
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Vascular Biology and Vascular Medicine
  • Ippei Watanabe, Junko Tatebe, Shunji Namba, Masayuki Koizumi, Junichi ...
    2013 Volume 77 Issue 1 Pages 224-230
    Published: 2013
    Released on J-STAGE: December 25, 2012
    Advance online publication: October 04, 2012
    JOURNAL FREE ACCESS
    Background: Indoxyl sulfate (IS) is a uremic toxin that causes renal injury, but little is known about its adverse effects on the cardiovascular system. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcriptional factor that mediates adaptive and toxic responses in cells. Recent studies identified IS as an endogenous agonist for AhR, as well as other tryptophan metabolites. The aim of the study was to investigate whether IS activates AhR, with subsequent inflammatory responses contributing to the development of atherogenesis, in human umbilical vein endothelial cells (HUVECs). Methods and Results: We demonstrated that IS stimulates the expression of AhR target genes, including cytochromes P450 1A1 and 1B1 mRNA, in a time-dependent manner, as well as translocation of AhR into the nucleus from the cytoplasm, indicating AhR activation. IS-stimulated AhR activation was accompanied by an increase in oxidative stress, proven by enhanced NADPH oxidase 4 expression and dihydroethidium staining. Additionally, AhR inhibitors abolished the IS-induced increase in monocyte chemoattractant protein-1 (MCP-1) expression in a dose-dependent manner. Taken together, these results suggest that IS activates AhR as an endogenous agonist and induces MCP-1 expression through reactive oxygen species production in HUVECs. Conclusions: Our findings give a novel understanding of the physiological effect of IS on the cardiovascular system and indicate possibilities for preventing cardiorenal syndrome by regulating serum IS levels.  (Circ J 2013; 77: 224–230)
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