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S100B: Role in cardiac remodeling and function following myocardial infarction in diabetes

机译:S100B:糖尿病心肌梗死在心脏重构和功能中的作用

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Aim: S100B plays a role in cardiac remodeling following myocardial infarction (MI) and in diabetic vascular complications but not examined in diabetic myocardium. We thus examined the effects of targeted deletion of S100B gene on post-MI hearts. Main methods: Coronary artery ligation or sham was performed 15 weeks after streptozotocin (STZ) or vehicle injection in wild-type (WT) and S100B knockout (BKO) mice. Left ventricular (LV) structural and functional remodeling was studied 35 days after induction of MI. Key findings: In diabetes, post-MI remodeling exhibited an attenuated increase in LV mass, dilation, and myocyte hypertrophy in association with increased apoptosis and fibrosis and reduced matrix metalloproteinase-2 (MMP-2) activity. Despite reduced LV dilation, impairment of cardiac function was similar to non-diabetic controls. Both diabetes and MI alone induced myocardial S100B and its canonical receptor for advanced glycation end product (RAGE) expression. By contrast, in post-MI diabetic myocardium, S100B expression was attenuated. Diabetic BKO, following MI demonstrated increased ventricular dilation compared to WT, in association with greater impairment of cardiac function, GLUT4 expression and systemic AGE levels. Significance: These data suggest that S100B expression may serve to modulate cardiac metabolism and adverse consequences of AGE in diabetic post-MI remodeling and function. ? 2012 Elsevier Inc.
机译:目的:S100B在心肌梗死(MI)后的心脏重塑和糖尿病血管并发症中起作用,但未在糖尿病心肌中进行检查。因此,我们检查了S100B基因靶向缺失对MI后心脏的影响。主要方法:在野生型(WT)和S100B基因敲除(BKO)小鼠中,链脲佐菌素(STZ)或媒介物注射后15周进行冠状动脉结扎或假手术。 MI诱导35天后研究了左心室(LV)的结构和功能重塑。关键发现:在糖尿病中,心肌梗死后重塑表现出左室重量减少,扩张和心肌肥大减少,并伴有凋亡和纤维化增加以及基质金属蛋白酶2(MMP-2)活性降低。尽管左心室扩张减少,但心功能受损与非糖尿病对照组相似。单独的糖尿病和心肌梗塞均可诱导心肌S100B及其经典受体,从而促进糖基化终末产物(RAGE)的表达。相比之下,在MI后糖尿病心肌中,S100B表达减弱。与WT相比,MI后的糖尿病BKO表现出心室扩张增加,并伴有更大的心脏功能,GLUT4表达和全身性AGE水平损伤。启示:这些数据表明,S100B的表达可能在糖尿病性心肌梗死后重塑和功能中调节心脏代谢和AGE的不良后果。 ? 2012爱思唯尔公司

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