Functional analysis of Angiotensin Receptor Binding Protein in The Cardiovascular Regulation

我们假设心脏ATRAP与血管紧张素II 1型受体的比例下调参与了心肌肥厚的发病机制。为了验证这一假设，我们接下来产生了在α-肌球蛋白重链启动子的控制下，在心肌细胞中特异性表达ATRAP的转基因小鼠。在心脏特异的ATRAP转基因小鼠中，血管紧张素II治疗背景下的心肌肥大的发生、p38丝裂原活化蛋白激酶的激活以及肥大相关基因的表达完全被抑制，尽管转基因小鼠的血压在放射遥测上与对照小鼠没有显著差异。这些结果表明，ATRAP在体内的心肌细胞特异性过表达可消除慢性血管紧张素II诱导的心肌肥大，从而提示ATRAP可能成为治疗心肌肥厚的新靶点。

We hypothesized that a downregulation of the cardiac ATRAP to angiotensin II type 1 receptor ratio is involved in the pathogenesis of cardiac hypertrophy. To examine this hypothesis, we next generated transgenic mice expressing ATRAP specifically in cardiomyocytes under control of the α-myosin heavy chain promoter. In cardiac-specific ATRAP transgenic mice, the development of cardiac hypertrophy, activation of p38 mitogen-activated protein kinase, and expression of hypertrophy-related genes in the context of angiotensin II treatment were completely suppressed, in spite of there being no significant difference in blood pressure on radiotelemetry between the transgenic mice and littermate control mice. These results demonstrate that cardiomyocyte-specific overexpression of ATRAP in vivo abolishes the cardiac hypertrophy provoked by chronic angiotensin II infusion, thereby suggesting ATRAP to be a novel therapeutic target in cardiac hypertrophy.