Inflammation and oxidative stress play key roles in atherosclerotic plaque instability, and plaque rupture/erosion and subsequent thrombus formation constitute the principal mechanisms of total vessel occlusion and acute ST-elevation myocardial infarction (STEMI). Plaque disruption triggers the formation of initial platelet aggregates that grow in association with an increase in fibrin formation, leading to persistent coronary flow obstruction and blood coagulation. The fibrin network may trap large numbers of erythrocytes and inflammatory cells to form an erythrocyte-rich thrombus. In fact, previous clinical studies have shown that not only platelet-rich white thrombi, but also erythrocyte-rich red thrombi can be visualized using angioscopy in patients with acute coronary syndrome. Recently, the development of thrombus aspiration and distal protection devices has significantly improved the clinical outcomes of percutaneous intervention in STEMI patients and has enabled the evaluation of antemortem coronary artery thrombi. This is important because previous autopsy studies were unable to differentiate coronary thrombi responsible for myocardial ischemia from postmortem clots. Using frozen samples of aspirated thrombi and specific monoclonal antibodies, we investigated the cellular components of thrombi (platelets, erythrocytes, fibrin and inflammatory cells, such as myeloperoxidase-positive cells) and pathologically evaluated the relationships between erythrocyte-rich thrombi and inflammation, oxidative stress and clinical outcomes in STEMI patients. Therefore, this review article focuses on the efficacy of thrombus aspiration therapy and the components of aspirated intracoronary thrombi in STEMI patients and presents the results of recent studies regarding the relationship between the composition of aspirated intracoronary thrombi and clinical outcomes.

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Aim: Vascular calcification, a major complication of chronic kidney disease (CKD), refers to the mineralization of vascular smooth muscle cells (VSMCs), resulting from a phenotypic change towards osteoblast-like cells. Histone deacetylase inhibitors (HDIs), potential therapeutic agents for CKD, are known to promote the differentiation and mineralization of osteoblasts. In this study, we aimed to determine the effects of an HDI on the phenotypic change of VSMCs and the development of vascular calcification.
Methods: The effect of trichostatin A (TSA), an HDI, on human aortic smooth muscle cells (HASMCs) was determined. The mineralization of HASMCs was induced by inorganic phosphorus (Pi), and was confirmed by quantitation of Ca levels and by von Kossa staining. Furthermore, we examined the effect of alkaline phosphatase (ALP) suppression using siRNA on Pi-induced vascular calcification in the presence or absence of TSA.
Results: TSA increased the expression and activity of ALP in HASMCs at a concentration which showed an inhibitory effect of histone deacetylase (HDAC) activity but not on cell viability. Moreover, TSA promoted the Pi-induced mineralization of HASMCs. In addition, both phosphonoformic acid (PFA), which is a sodium-dependent phosphate transporter inhibitor, and suppression of ALP expression by siRNA markedly inhibited the TSA-promoted mineralization of HASMCs.
Conclusion: These data show that inhibition of HDAC activity promotes Pi-induced vascular calcification via the up-regulation of ALP expression. Taken together, HDIs may increase the risk of vascular calcification in CKD patients.

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Aim: Chronic kidney disease (CKD) is a known risk factor for cardiovascular disease (CVD). Cystatin C was recently reported to be an endogenous surrogate of kidney function, and a high level of cystatin C is reported to be a strong predictor of CVD; however, the association between cystatin C and arteriosclerosis in a non-CKD population is unclear. This study aimed to clarify the association between cystatin C and arteriosclerosis in a non-CKD population.
Methods: Of the 637 Japanese adults (264 men, 373 women) enrolled, we analyzed 446 participants with an estimated glomerular filtration rate (eGFR) >60 mL/min and no proteinuria (177 men, 269 women) without a history of CVD. Kidney function was evaluated according to serum cystatin C levels and eGFR. Arteriosclerosis was evaluated on the basis of the cardio-ankle vascular index (CAVI) and carotid intima-media thickness (CIMT).
Results: The mean age of our subjects was 67.0±10.0 years. No variables showed any significant differences according to gender. The results of multiple linear regression analysis showed a significant correlation between serum cystatin C and CAVI only in women, but not CIMT.
Conclusion: We observed a significant correlation between cystatin C and CAVI, which is a marker of early-stage arteriosclerosis, in women in a non-CKD population with no proteinuria and eGFR>60 mL/min.

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Aim: The cardio-ankle vascular index (CAVI) is an index of arterial stiffness. We investigated the association of CAVI with the severity of coronary artery calcification (CAC) and coronary stenosis by coronary computed tomography angiography (CTA) in an asymptomatic population.
Methods: A total of 549 asymptomatic Korean individuals who underwent CAVI and CTA were analyzed retrospectively. CAC and coronary stenosis were measured by CTA and assessed for the correlation with CAVI.
Results: The degree of CAC and coronary stenosis demonstrated a significant correlation with CAVI (r= 0.187, p<0.001 and r= 0.212, p<0.001 for the CAC score and stenosis, respectively). After adjustment for potential confounders, including age, gender, hypertension, diabetes mellitus, and dyslipidemia, a predefined cutoff value of CAVI ≥8 was associated with advanced CAC (CAC ≥300) and significant coronary stenosis (stenosis ≥50%). Specifically, the adjusted odds ratio (95% confidence interval) of CAC ≥300 and coronary stenosis ≥50% was 3.57 (1.92-6.66) and 2.81 (1.13-7.00), respectively. Additional inclusion of CAVI improved the predictive power of the receiver operating characteristic curves for predicting coronary atherosclerosis based on traditional risk factors; the area under the curve for predicting CAC ≥300 and coronary stenosis ≥50% increased from 0.739 to 0.791 (p for difference= 0.023), and from 0.761 to 0.842 (p= 0.032), respectively.
Conclusions: CAVI reflects coronary atherosclerosis and may be used as a screening tool for assessing subclinical atherosclerotic burden in an asymptomatic population.

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Aim: Although higher adiponectin levels predict a low risk of type 2 diabetes, elevated adiponectin levels predict higher mortality in older persons.
Methods: We examined the associations of adiponectin with anthropometric, metabolic and hematological variables and renal function in 361 community-dwelling elderly women aged 76±8. Renal function was assessed using the estimated glomerular filtration rate (eGFR).
Results: By univariate analysis, hemoglobin (r=−0.307, p<0.001) and creatinine-based eGFR (r=−0.121, p<0.05) were inversely associated with adiponectin. After adjustment for percentage body fat, HDL cholesterol and serum leptin, hemoglobin and creatinine-based eGFR remained independent predictors of adiponectin (standardized β coefficient=−0.248, p<0.0001, and −0.101, p=0.03, respectively). A similar but stronger relationship was observed between adiponectin and cystatin C-based eGFR (standardized β coefficient=−0.180, p=0.02).
Elderly women with anemia had higher serum adiponectin than those without anemia (17.7±9.1 vs. 14.1±7.0 µg/mL, p=0.001). Women with creatinine-based eGFR <45 mL/min/1.73 m2 (19.2±10.6 µg/mL) had higher adiponectin than those with eGFR ≥45 −< 60 mL/min/1.73 m² (14.4±6.9 µg/mL) and those with eGFR ≥60 mL/min/1.73 m² (14.5±7.4 µg/mL, p<0.05).
Conclusions: We conclude that hemoglobin and eGFR are independently associated with serum adiponectin in community-dwelling elderly women. Anemia and reduced renal function may contribute to elevated adiponectin levels in the elderly and may represent important confounders of the relationship between elevated adiponectin and mortality in this population.

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Aim: We aimed to study the relationship of elevated C reactive protein (CRP) levels (1.0-2.9 or ≥3.0 mg/L) with carotid intima-media thickness (IMT) in Chinese adults with normal low-density lipoprotein (LDL) cholesterol (<100 mg/dL).
Methods: Cross-sectional analysis was performed using 2499 eligible subjects recruited from a single community in Shanghai in 2008. These subjects were divided into three groups according to their serum CRP levels (<1.0 mg/L, 1.0-2.9 and ≥3.0 mg/L). IMT was measured using a high-resolution tomographic ultrasound system.
Results: As compared to CRP <1.0 mg/L (n= 1994), subjects with CRP 1.0-2.9 (n=265) and ≥3.0 mg/L (n= 240) were much older and had higher body mass index, waist circumference, systolic and diastolic blood pressure, hemoglobin A1c and serum triglycerides; IMT was significantly elevated in CRP ≥3.0 or 1.0-2.9 mg/L (0.66 or 0.65 vs 0.61 mm, p<0.0001). Subjects with CRP ≥3 mg/L were associated with 1.45-fold risk for elevated IMT (≥0.7 mm) (95% confidence interval, 1.02-2.06) after full adjustment. The association was more prominent in subjects with aged <60 (odds ratio (OR)= 2.04; p= 0.04), in diabetic patients (OR= 1.79; p= 0.04) and obese subjects (OR= 1.55; p= 0.006).
Conclusions: Increased CRP is associated with elevated IMT in Chinese adults with normal LDL. Low-grade inflammation plays an independent and important role in atherosclerosis.

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Aim: Smoking induces vascular inflammation and increases the risk of cardiovascular events. Lectinlike oxidized low-density lipoprotein receptor-1 (LOX-1) is a scavenger receptor that is induced by oxidative stress and is associated with atherosclerotic plaque formation and destabilization. LOX-1 interacts with C-reactive protein (CRP) and plays an important role in inflammatory diseases. We therefore hypothesized that LOX-1 may be involved in the onset of smoking-induced vascular inflammation.
Methods: We measured the soluble LOX-1 (sLOX-1) levels in sera obtained from 207 current smokers.
Results: The serum sLOX-1 levels positively correlated with various smoking variables, such as the number of cigarettes smoked per day (r= 0.150, p<0.05), the expired air carbon monoxide (CO) concentrations (r= 0.198, p<0.005) and the Fagerstrom test for nicotine dependence scores (r= 0.190, p<0.01). The serum levels of sLOX-1 also correlated with those of a representative inflammatory marker, the serum high-sensitivity CRP level (hsCRP; r= 0.232, p<0.005). A multivariate regression analysis revealed the independent determinants of the serum sLOX-1 level to be the expired air CO concentration (β= 0.182, p<0.05) and the hsCRP level (β= 0.213, p<0.01).
Conclusions: The serum sLOX-1 level was found to increase in close association with both the smoking-related variables and the inflammatory marker hsCRP. These findings suggest that LOX-1 may therefore play an important role in the onset of smoking-induced inflammation and atherosclerosis in humans.

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Aim: To investigate the acute effects of the simultaneous ingestion of fructose and fat on postprandial lipoprotein metabolism in healthy young women.
Methods: Nine young healthy Japanese women with a normal weight (body mass index: 18.5≤−< 25 kg/m²), a normal ovarian cycle and an apolipoprotein E 3/3 phenotype were enrolled as participants and studied on four occasions. At each session, the subjects ingested one of four beverages containing either glucose or fructose (0.5 g/kg body weight each) with or without OFTT cream (1 g/kg, 0.35 g/ kg as fat) in a randomized crossover design. Blood samples were collected at baseline and at 0.5, 1, 2, 4 and 6 hours after ingestion.
Results: The ingestion of fructose combined with fat led to significantly higher rises in the serum triglyceride (TG), remnant-like particle (RLP)-TG, remnant lipoprotein-cholesterol (RemL-C) and apolipoprotein B-48 (apoB48) concentrations with delayed peaks compared with that observed following ingestion of the other three types of beverages. The incremental area under the curve (ΔAUC)-TG and ΔAUC-apoB48 were larger than those observed for the ingestion of fat only. The serum RLP-TG and apoB48 concentrations returned to the fasting levels (0 hours) at the end of the test (6 hours) following the ingestion of fat only; however, these concentrations did not return to the fasting levels following the intake of fructose combined with fat.
Conclusions: These findings suggest a delay in the clearance of intestinal TG-rich lipoproteins, namely chylomicron and its remnant, following the ingestion of fructose combined with fat. The simultaneous ingestion of fructose and fat markedly enhances postprandial exogenous lipidemia in young healthy Japanese women.

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