Functional, structural and molecular aspects of diastolic heart failure in the diabetic (mRen-2)27 rat
Functional, structural and molecular aspects of diastolic heart failure in the diabetic (mRen-2)27 rat
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DOI：
10.1016/j.cardiores.2007.06.022
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发表时间：
2007-11-01
影响因子：
10.8
通讯作者：
Gilbert, R. E.
中科院分区：
文献类型：
--
作者：
Connelly, K. A.;Kelly, D. J.;Gilbert, R. E.
目的：糖尿病性心肌病是一个日益被认识到的心力衰竭的原因，尽管保留左心室收缩功能。鉴于血管紧张素11在人糖尿病心肌病中的过度表达，我们假设在啮齿动物模型中，高血压与增强的组织肾素-血管紧张素系统相结合将导致舒张功能障碍和不良重构的发展。研究方法：将纯合子（mRen-2）27只大鼠和非转基因Sprague道利（SD）大鼠随机接受链脲佐菌素（糖尿病）或载体（非糖尿病），并随访6周。在组织收集之前，动物经历压力-容积环采集。结果如下：糖尿病Ren-2大鼠出现了主动和被动相的阿糖胞苷受损，伴随着SERCA-2a ATP酶和受磷蛋白沿着胎儿基因程序的激活而减少。Ren-2大鼠糖尿病性心肌病的结构特征包括间质纤维化、心肌细胞肥大和凋亡以及转化生长因子-β活性增加（3（p
Objective: Diabetic cardiomyopathy is an increasingly recognized cause of cardiac failure despite preserved left ventricular systolic function. Given the over-expression of angiotensin 11 in human diabetic cardiomyopathy, we hypothesized that combining hyperglycaemia with an enhanced tissue renin-angiotensin system would lead to the development of diastolic dysfunction with adverse remodeling in a rodent model. Methods: Homozygous (mRen-2)27 rats and non-transgenic Sprague Dawley (SD) rats were randomized to receive streptozotocin (diabetic) or vehicle (non-diabetic) and followed for 6 weeks. Prior to tissue collection, animals underwent pressure-volume loop acquisition. Results: Diabetic Ren-2 rats developed impairment of both active and passive phases of diastole, accompanied by reductions in SERCA-2a ATPase and phospholamban along with activation of the fetal gene program. Structural features of diabetic cardiomyopathy in the Ren-2 rat included interstitial fibrosis, cardiac myocyte hypertrophy and apoptosis in conjunction with increased activity of transforming growth factor-beta(3 (p