Liesmaa Inka, Kuoppala Antti, Shiota Naotaka, Kokkonen Jorma O, Kostner Karam, Mäyränpää Mikko, Kovanen Petri T, Lindstedt Ken A
Wihuri Research Institute, Helsinki, Finland.
Am J Physiol Heart Circ Physiol. 2005 May;288(5):H2317-22. doi: 10.1152/ajpheart.00815.2004.
In experimental animals, bradykinin type-1 receptors (BK-1Rs) are induced during inflammation and ischemia, and, by exerting either cardioprotective or cardiotoxic effects, they may contribute to the pathogenesis of heart failure. Nothing is known about the expression of BK-1Rs in human heart failure. Human heart tissue was obtained from excised hearts of patients undergoing cardiac transplantation (n = 13), due to idiopathic dilated cardiomyopathy (IDC; n = 7) or to coronary heart disease (CHD; n = 6), and from normal hearts (n = 6). The expression of BK-1Rs was analyzed by means of competitive RT-PCR, Western blot analysis, and immunohistochemistry. Expression of BK-1R mRNA was increased in both IDC (2.8-fold) and CHD (2.1-fold) hearts compared with normal hearts. The observed changes were verified at the protein level. Expression of BK-1Rs in failing hearts localized to the endothelium of intramyocardial coronary vessels and correlated with an increased expression of TNF-alpha in the vessel wall. Treatment of human coronary artery endothelial cells with TNF-alpha increases their BK-1R expression. These novel results show that BK-1Rs are induced in the endothelium of intramyocardial coronary vessels in failing human hearts and so may participate in the pathogenesis of heart failure.
在实验动物中，缓激肽1型受体（BK-1Rs）在炎症和缺血过程中被诱导，并且通过发挥心脏保护或心脏毒性作用，可能参与心力衰竭的发病机制。关于BK-1Rs在人类心力衰竭中的表达情况尚无相关报道。从因特发性扩张型心肌病（IDC；n = 7）或冠心病（CHD；n = 6）而接受心脏移植的患者切除的心脏（n = 13）以及正常心脏（n = 6）中获取人类心脏组织。通过竞争性逆转录聚合酶链反应、蛋白质印迹分析和免疫组织化学方法分析BK-1Rs的表达。与正常心脏相比，IDC心脏（2.8倍）和CHD心脏（2.1倍）中BK-1R mRNA的表达均增加。在蛋白质水平证实了观察到的变化。衰竭心脏中BK-1Rs的表达定位于心肌内冠状动脉的内皮细胞，并且与血管壁中肿瘤坏死因子-α（TNF-α）表达增加相关。用TNF-α处理人冠状动脉内皮细胞会增加其BK-1R表达。这些新结果表明，BK-1Rs在衰竭的人类心脏心肌内冠状动脉内皮细胞中被诱导，因此可能参与心力衰竭的发病机制。
