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首页> 外文期刊>Circulation journal >Overexpression of human C-reactive protein exacerbates left ventricular remodeling in diabetic cardiomyopathy.
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Overexpression of human C-reactive protein exacerbates left ventricular remodeling in diabetic cardiomyopathy.

机译：在糖尿病性心肌病中，人类C反应蛋白的过表达加剧了左心室重构。

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BACKGROUND: C-reactive protein (CRP) is known to be a pathogenic agent in the cardiovascular system. However, the effect of CRP on heart failure has not been elucidated. The effect of human CRP on cardiac dysfunction induced by diabetes mellitus (DM) using human CRP-overexpressing transgenic mice (CRP-Tg) was examined. METHODS AND RESULTS: DM was induced in male wild-type mice (Wt/DM) and CRP-Tg (CRP/DM) by an injection of streptozotocin. Non-diabetic wild-type mice (Wt/Con) and CRP-Tg (CRP/Con) served as controls. Echocardiography and hemodynamic measurements 6 weeks after injection showed lower fractional shortening and left ventricular (LV) dP/dt max in CRP/DM compared with Wt/DM. Myocardial mRNA levels of interleukin-6, tumor necrosis factor-alpha, plasminogen activator inhibitor-1, angiotensin type 1 receptor, angiotensinogen, NADPH oxidase subunits (p47(phox), gp91(phox)), glutathione peroxidase-3. and connective tissue growth factor were increased in CRP/DM compared with Wt/DM. Nuclear staining of 8-hydroxydeoxyguanosine was also increased in CRP/DM compared with Wt/DM. CRP/DM was associated with increased terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling positive cells and a higher ratio of Bax/Bcl-2 proteins compared with Wt/DM. The extent of cardiac fibrosis assessed by Sirius red staining and immunohistochemical staining for collagen type 1 was significantly increased in CRP/DM compared with Wt/DM. CONCLUSIONS: Overexpression of human CRP exacerbates LV dysfunction and remodeling in diabetic cardiomyopathy, possibly through enhancement of the inflammation, renin-angiotensin system, and oxidative stress.
机译：背景：C反应蛋白（CRP）是心血管系统中的致病因子。但是，尚未阐明CRP对心力衰竭的作用。使用人CRP过表达的转基因小鼠（CRP-Tg）检测了人CRP对糖尿病（DM）诱发的心脏功能障碍的影响。方法与结果：注射链脲佐菌素可在雄性野生型小鼠（Wt / DM）和CRP-Tg（CRP / DM）中诱导DM。非糖尿病野生型小鼠（Wt / Con）和CRP-Tg（CRP / Con）作为对照。注射后6周的超声心动图和血流动力学测量结果显示，与Wt / DM相比，CRP / DM的缩短分数缩短和左心室（LV）dP / dt max降低。心肌白细胞介素6，肿瘤坏死因子-α，纤溶酶原激活物抑制剂1，血管紧张素1型受体，血管紧张素原，NADPH氧化酶亚基（p47（phox），gp91（phox）），谷胱甘肽过氧化物酶3的mRNA水平。与Wt / DM相比，CRP / DM中的组织和结缔组织生长因子增加。与Wt / DM相比，CRP / DM中8-羟基脱氧鸟苷的核染色也增加了。与Wt / DM相比，CRP / DM与末端脱氧核苷酸转移酶介导的dUTP缺口末端标记阳性细胞增多和Bax / Bcl-2蛋白比率更高有关。与Wt / DM相比，在CRP / DM中，通过Sirius红染色和1型胶原免疫组织化学染色评估的心脏纤维化程度显着增加。结论：人CRP的过度表达可能加剧炎症，肾素-血管紧张素系统和氧化应激，从而加剧糖尿病性心肌病的左室功能障碍和重塑。

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