Kuoppala Antti, Shiota Naotaka, Kokkonen Jorma O, Liesmaa Inka, Kostner Karam, Mäyränpää Mikko, Kovanen Petri T, Lindstedt Ken A
Wihuri Research Institute, Helsinki, Finland.
J Am Coll Cardiol. 2002 Jul 3;40(1):119-25. doi: 10.1016/s0735-1097(02)01928-9.
We sought to study the expression of bradykinin type-2 receptors (BK-2Rs) in patients with heart failure (HF).
Recent work in experimental animals has suggested that bradykinin (BK) exerts cardioprotective effects through specific BK-2Rs. However, nothing is known about the regulation of BK-2R expression in the pathogenesis of human HF.
Human heart tissue was obtained from excised hearts of patients undergoing cardiac transplantation (n = 13) and from normal hearts (n = 6) unsuitable for donation. The patients had HF due to idiopathic dilated cardiomyopathy (IDC) (n = 7) or coronary heart disease (CHD) (n = 6). Tissue samples from the left ventricles were analyzed by competitive reverse-transcriptase-polymerase chain reaction and Western blotting for the expression of BK-2R messenger ribonucleic acid (mRNA) and protein.
In both the IDC and CHD hearts, the level of BK-2R mRNA expression was found to be significantly lower (30% and 38% of control values, respectively) than that in normal hearts. Correspondingly, the BK-2R protein level was significantly reduced in both the IDC and CHD hearts (45% and 62% of control values, respectively) and apparently involved all myocardial cell types. The down-regulation of BK-2R expression in failing hearts did not correlate with decreased cellularity or with the expression pattern of other members of the G-protein-coupled receptor superfamily. However, BK-2R down-regulation in the failing hearts was associated with a decrease in endothelial nitric oxide synthase in both IDC (53% of control value) and CHD (43% of control value) hearts.
These results are the first to suggest that a loss of BK-2Rs is involved in the pathogenesis of human HF.
我们试图研究缓激肽2型受体（BK-2Rs）在心力衰竭（HF）患者中的表达情况。
最近在实验动物中的研究表明，缓激肽（BK）通过特定的BK-2Rs发挥心脏保护作用。然而，关于BK-2R表达在人类HF发病机制中的调控情况尚无定论。
从接受心脏移植患者（n = 13）切除的心脏以及不适合捐赠的正常心脏（n = 6）中获取人类心脏组织。这些患者因特发性扩张型心肌病（IDC）（n = 7）或冠心病（CHD）（n = 6）导致HF。通过竞争性逆转录聚合酶链反应和蛋白质印迹法分析左心室组织样本中BK-2R信使核糖核酸（mRNA）和蛋白质的表达。
在IDC和CHD心脏中，均发现BK-2R mRNA表达水平显著低于正常心脏（分别为对照值的30%和38%）。相应地，IDC和CHD心脏中的BK-2R蛋白水平均显著降低（分别为对照值的45%和62%），且明显涉及所有心肌细胞类型。衰竭心脏中BK-2R表达的下调与细胞数量减少或G蛋白偶联受体超家族其他成员的表达模式无关。然而，衰竭心脏中BK-2R的下调与IDC（对照值的53%）和CHD（对照值的43%）心脏中内皮型一氧化氮合酶的减少有关。
这些结果首次表明BK-2Rs的缺失参与了人类HF的发病机制。
