The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Volume 222, Issue 3
Displaying 1-10 of 10 articles from this issue
Regular Contributions
  • Haitao Li, Yu Liu, He Huang, Yanhong Tang, Bo Yang, Congxin Huang
    2010 Volume 222 Issue 3 Pages 167-174
    Published: 2010
    Released on J-STAGE: October 21, 2010
    Ventricular arrhythmia in chronic heart failure (CHF) is considered to be associated with stimulation of β-adrenergic receptors (β-ARs). Three classes of β-ARs have been identified; importantly, distinct from β1 and β2 subtypes, β3-AR could inhibit arrhythmia. Intracellular Ca2+ is considered as a predominant effecter of arrhythmia during heart failure. However, the exact role of β3-AR in arrhythmia and Ca2+ regulation in CHF is not clear yet. Therefore, we studied the effect of BRL37344, a specific β3-AR activator, on CHF-related ventricular arrhythmia and cellular Ca2+ transport. Rabbits with CHF induced by combined aortic insufficiency and aortic constriction were treated with BRL37344 in the presence or absence of β1-AR and β2-AR stimulation. We then evaluated the current produced by sodium calcium exchanger (INCX), an electrical marker of abnormal Ca2+ removal through ion transporter protein sodium calcium exchanger (NCX), Ca2+ transient, a sign of Ca2+ entering the cell, concentration of Ca2+ in sarcoplasmic reticulum (SR) (SR Ca2+ load) and its abnormal release (SR Ca2+ leak). After treatment with BRL37344, the incidence of ventricular arrhythmias induced by infusion of a β1-AR or β2-AR activator decreased significantly. Similarly, β3-AR stimulation remarkably inhibited increase of INCX, Ca2+ transient, SR Ca2+ load and leak induced by activation of β1-AR or β2-AR. SR59230A, a specific β3-AR blocker, abolished the inhibitory effects of BRL37344. These results suggest that β3-AR activation could inhibit ventricular arrhythmia through regulating intracellular Ca2+. Thus, β3-AR is a feasible therapeutic target that holds promise in the treatment of ventricular arrhythmias in CHF.
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  • Takafumi Kato, Nobuyuki Ohte, Kazuaki Wakami, Toshihiko Goto, Hidekats ...
    2010 Volume 222 Issue 3 Pages 175-181
    Published: 2010
    Released on J-STAGE: October 26, 2010
    When one bends the elbow by shortening of the biceps, a knot of muscle is observed in his or her upper arm, indicating that muscle shortening is converted to muscle standing in the perpendicular direction due to the incompressibility of skeletal muscle. A similar mechanism may work in the thickening process of the left ventricular (LV) wall. Although myocardial fibers of the left ventricle shorten by about 20% along the fiber direction when they contract, thickening of the LV wall during contraction often exceeds 50%. Thus, the aim of the present study was to clarify the mechanism by which myocardial fiber shortening produces such remarkable thickening of the LV wall. We hypothesized that myocardial fiber shortening in the circumferential direction causes myocardial transformation perpendicular to the fiber direction, thereby producing LV wall thickening. We evaluated this hypothesis using an incompressible model of the LV wall. In 15 healthy male volunteers (38 ± 13 years), we calculated theoretical peak thickening values of the inner and outer LV wall layers and compared them with directly measured peak thickening values using Doppler strain imaging at the corresponding areas. The theoretical peak thickening and directly measured peak thickening were > 60% in the LV inner layer. The theoretical peak thickening was correlated with the directly measured peak thickening in the inner (r = 0.75, p < 0.05) and outer (r = 0.61, p < 0.05) layers. We conclude that shortening of LV circumferential myocardial fiber and incompressibility of myocardium produce LV wall thickening during contraction.
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  • Züleyha Akkan Çetinkaya, Mesut Sezikli, Fatih Güzelbu ...
    2010 Volume 222 Issue 3 Pages 183-186
    Published: 2010
    Released on J-STAGE: October 27, 2010
    The risks of prostate cancer and colorectal carcinoma increase with age. So, colonoscopy and measurement of serum prostate specific antigen (PSA) may be performed during a short term in a given patient. We aimed to evaluate whether colonoscopy affects serum PSA levels and to evaluate the relationship between prostate volume and elevation in serum PSA levels after colonoscopy. This study included 44 consecutive male patients, who underwent colonoscopy. The mean age of the patients was 56.05 ± 9.27 years. The mean time required for colonoscopy was 30 min. Serum PSA levels were measured 48-72 hours before colonoscopy, immediately after performing laxative enema, and at 24-48th hour, the 7th day, and the 14th day after colonoscopy in each patient. The serum PSA level was elevated after enema and at 24-48th hour and 7th day after colonoscopy from the baseline (p < 0.05), and declined to the baseline by 14th day. When the cut off value of 20 cm3 for normal prostate volume was taken into account, the serum PSA levels were significantly higher at the 24-48th hour and the 7th day in patients with larger prostate volume (> 20 cm3) than those with normal prostate volume (p = 0.013 and p = 0.009). These results suggest that PSA is easily released by manipulations from the larger prostate. In conclusion, serum PSA levels were elevated during 7 days after colonoscopy. Before performing invasive procedures, patients with high serum PSA levels should be asked whether colonoscopy was performed prior to the measurement.
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  • Guang Liu, Ying Huang, Xinwu Lu, Min Lu, Xintian Huang, Weimin Li, Mie ...
    2010 Volume 222 Issue 3 Pages 187-193
    Published: 2010
    Released on J-STAGE: October 26, 2010
    Abdominal aortic aneurysm (AAA) is a lethal disease, occurring mostly in men more than 65 years of age. Until recently, the pathogenesis of AAA remains poorly understood. MicroRNAs (miRNAs) are a novel class of endogenous small non-coding RNAs that play important roles in diverse biological and pathological processes including cardiovascular diseases. However, their biological roles in AAA formation have not been elucidated. In this study, we employed oligonucleotide microarrays to detect and compare miRNA expression profiles in a rat model of AAA. The abdominal aorta was exposed and incubated for 20 min with saline supplemented with calcium chloride and collagenase. After 28 days, the treated aortas were evaluated by digital measurement and angiography. A 50% increase over the normal diameter is considered as AAA. Our results revealed a set of differentially expressed miRNAs, with 10 significantly up-regulated and 5 significantly down-regulated miRNAs in AAA tissues. Four miRNAs (miR-19a, miR-19b, miR-132, and miR-221) were randomly selected for validation using real-time RT-PCR. Functional annotations of all putative targets of differentially expressed miRNAs via bioinformatics approaches revealed that predicted targets were highly enriched and involved in several key signaling pathways important for AAA formation, including pathways in cancer and signaling pathways involving mitogen-activated protein kinase, Wnt, neurotrophin, and ErbB. In summary, this study indicates that miRNAs might contribute to AAA formation probably by affecting multiple target genes and signaling pathways, which is expected to provide new clues to develop targeted therapies against this calamitous disease.
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  • Jian-Guo Hu, He-Zuo Lü, Yan-Xia Wang, Ming-Sheng Bao, Bao-Ming Zh ...
    2010 Volume 222 Issue 3 Pages 195-200
    Published: 2010
    Released on J-STAGE: October 29, 2010
    Oligodendrocyte precursor cells (OPCs) can differentiate into oligodendrocytes or astrocytes, depending on cellular microenvironments. OPCs, cultured in medium supplemented with 10% (v/v) fetal bovine serum (FBS), give rise to type II astrocytes that express glial fibrillary acidic protein and a cell surface ganglioside that is recognized by A2B5 monoclonal antibody. However, the factors in FBS that direct the astrocyte differentiation are not determined. Moreover, bone morphogenetic proteins (BMPs) have been reported to be involved in astrocyte differentiation of neural progenitor cells. We therefore examined whether BMPs are responsible for the serum-mediated astrocyte differentiation from OPCs. OPCs were isolated from the spinal cords of Wistar rat embryos (at day 14) using the A2B5 antibody. We measured the concentrations of BMP-2 and BMP-4 in FBS and rat and human sera and the expression of mRNAs for three types of BMP receptors (BMPRIa, Ib and II) in OPCs by RT-PCR. The serum samples of the three species contained BMP-2 and BMP-4, as judged by ELISA with each monoclonal antibody, and the BMP receptor mRNAs are expressed in OPCs. When OPCs were cultured in the medium containing 10% FBS, cells (more than 95%) differentiated into type II astrocytes. However, when OPCs were pretreated with noggin, a soluble antagonist of BMP action, the degree of astrocyte differentiation was markedly decreased from 95.39 to 38.36%. Taken together, these results suggest that BMP signaling may be responsible for the serum-mediated astrocyte differentiation of OPCs. Our findings provide new insights into the molecular basis of differentiation of OPCs.
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  • Koichiro Sugimura, Yoshihiro Fukumoto, Jun Nawata, Huan Wang, Noriko O ...
    2010 Volume 222 Issue 3 Pages 201-210
    Published: 2010
    Released on J-STAGE: November 05, 2010
    Atherosclerosis is initiated by adhesion and infiltration of inflammatory leukocytes into the intima, where non-receptor protein tyrosine kinases, such as focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (PYK2), play important roles as intracellular messengers of mechanical and biochemical signals. In the present study, we examined whether FAK and PYK2 are up-regulated by elevated blood pressure or circulating humoral factors in hypertension. We used a rat model of abdominal aortic banding that allows separate evaluation of elevated blood pressure (upper body) and circulating humoral factors (lower body). We obtained the proximal and distal aortas of the banding site, 6 hours, 3 days, and 1 and 4 weeks after the banding procedure, for evaluation of phosphorylation of FAK and PYK2 by Western blotting. Arterial pressure was significantly elevated only in the upper body throughout the experimental period. The expression of FAK and the FAK phosphorylation were significantly increased at 1 and 4 weeks only in the proximal aorta. This was also the case for the expression of total PYK2 and the PYK2 phosphorylation. In contrast, there was no significant change in FAK or PYK2 phosphorylation in the distal aorta, whereas plasma levels of angiotensin II were systemically elevated. In sham-operated rats, no change in FAK or PYK2 phoshorylation was noted in the proximal and distal aortas. These results indicate that phosphorylation of FAK and PYK2 is upregulated by elevated blood pressure but not by humoral factors in the rat aorta, demonstrating novel aspects of atherogenesis in hypertension.
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  • Jie Cheng, Yanling Wang, Zilu Wang, Mifang Yang, Yunong Wu
    2010 Volume 222 Issue 3 Pages 211-218
    Published: 2010
    Released on J-STAGE: October 29, 2010
    Proteoglycan 4 (PRG4) is a multifaceted glycoprotein that mediates boundary lubrication of articular cartilage and its dysregulation is associated with impaired lubrication and cartilage destruction in multiple synovial joints. However, the spatiotemporal expression of PRG4 and the associated regulatory networks remain largely unknown in the mandibular condylar cartilage that is responsible for homeostasis and functions of the temporomandibular joint. We here investigated the possible regulatory effects of the interleukin-1α (IL-1α) or/and transforming growth factor-β1 (TGF-β1) on the expression of PRG4 in primary chondrocytes that were isolated from the superficial layer of the condylar cartilage of the 20-day-old male Sprague-Dawley rats. Both IL-1α and TGF-β1 have been implicated in joint destruction and repair. Treatment of primary chondrocytes for 24 h with recombinant human (rh) IL-1α (10 ng/ml) resulted in pronounced reduction in the expression levels of PRG4 mRNA and protein, whereas stimulation with rhTGF-β1 (10 ng/ml) significantly increased the expression levels, as measured by RT-PCR and ELISA, respectively. Moreover, rhTGF-β1 was capable to antagonize the inhibitory effects on the PRG4 expression caused by rhIL-1α and robustly restored its abundance in the cultured condylar chondrocytes. Taken together, our data indicate that PRG4 is synthesized and secreted by condylar cartilage chondrocytes and its expression is differentially regulated by IL-1α and TGF-β1. The rhIL-1α-mediated PRG4 repression is reversible and potently antagonized by rhTGF-β1 in condylar chondrocytes. The observed up-regulation of PRG4 upon rhTGF-β1 treatment further supports the therapeutic application of rhTGF-β1 in the treatment of temporomandibular joint osteoarthritis.
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  • Shu-Qin Liu, Yan-Yun Yu, Hong-Wen Xie, Ke Yu, Le-Xin Wang
    2010 Volume 222 Issue 3 Pages 219-223
    Published: 2010
    Released on J-STAGE: November 10, 2010
    Re-stenosis or remodeling of coronary and peripheral arteries remains a major complication following balloon-angioplasty or stenting. This study was designed to investigate the effect of nesiritide, a recombinant B-type natriuretic peptide (BNP), on vascular remodeling following balloon-induced endothelial injuries. Twenty-eight male New Zealand rabbits were divided into nesiritide-treated (0.1 mg/kg/day, sc, for 4 weeks, n = 10), saline-treated control (n = 10) and sham-operated groups (n = 8). In the nesiritide and control groups, a balloon catheter was inserted to the right iliac artery to induce injuries. Vascular endothelial growth factor (VEGF) was measured by immunohistochemistry. The area under internal elastic membrane of the arterial wall (643.2 ± 134.1 vs 493.7 ± 139.3 μm2, p < 0.05) and the area under external elastic membrane (1495.1 ± 204.9 vs 1265.9 ± 232.6 μm2, p < 0.05) in the nesiritide group were greater than those in the control group, but were smaller than those in the sham-operated group (p < 0.05). The stenosis ratio was lower in the nesiritide group than in the control group (18.7 ± 7.7% vs 38.0 ± 8.3%, p < 0.01). Importantly, the VEGF expression rate was significantly lower in the nesiritide group than in the control group (42.2 ± 8.8% vs 56.1 ± 13.1%, p < 0.05), while there were no signs of VEGF expression in the non-injured arteries of the three groups. In conclusion, nesiritide treatment reduces the stenosis of the rabbit iliac artery following balloon-induced endothelial injuries probably by decreasing VEGF expression.
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Letter to the Editor