Protease corin expression and activity in failing hearts
Protease corin expression and activity in failing hearts
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DOI：
10.1152/ajpheart.00399.2010
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发表时间：
2010-11-01
影响因子：
4.8
通讯作者：
Wu, Qingyu
中科院分区：
文献类型：
--
作者：
Chen, Shenghan;Sen, Subha;Wu, Qingyu
陈S，森S，杨D，王W，莫拉维克CS，吴Q。衰竭心脏中蛋白酶corin的表达和活性。Am J Physiol Heart Circ Physiol 299：H1687-H1692，2010.首次发表于2010年8月27日; doi：10.1152/ajpheart.00399.2010.-心钠素和脑钠素（ANP和BNP）调节血压和心脏功能。在心力衰竭（HF）患者中，血浆前体ANP和BNP的前体形式pro-ANP和pro-BNP水平高度升高，但利钠肽加工明显不足的机制尚不清楚。Corin是一种激活利钠肽的心脏蛋白酶。在这项研究中，我们检测了corin蛋白在小鼠和人类衰竭心脏中的表达和活性。组织样本来自肌营养因子过度表达诱导的HF小鼠模型和人非衰竭、肥厚和衰竭心脏。通过Western印迹和ELISA测量膜级分和组织裂解物中的Corin蛋白水平。Corin催化和生物活性通过荧光底物和pro-ANP加工测定来测量。在小鼠中，corin蛋白水平在正常心脏中并不随年龄变化，但在衰竭心脏中显著增加。在人类中，corin蛋白水平在非衰竭和衰竭心脏的心房中相似，但在衰竭心脏的心室中与非衰竭或肥厚心脏相比有所增加。然而，与蛋白质水平不同，corin活性在衰竭心脏中没有增加，通过荧光底物和前心钠素加工测定来测量。我们的研究结果表明corin激活是心脏衰竭的限速步骤。corin激活不足预期会阻止利钠肽加工，并可能导致HF患者体液潴留和心功能受损。
Chen S, Sen S, Young D, Wang W, Moravec CS, Wu Q. Protease corin expression and activity in failing hearts. Am J Physiol Heart Circ Physiol 299: H1687-H1692, 2010. First published August 27, 2010; doi:10.1152/ajpheart.00399.2010.-Atrial and brain natriuretic peptides (ANP and BNP) regulate blood pressure and cardiac function. In patients with heart failure (HF), plasma levels of pro-ANP and pro-BNP, the precursor forms of ANP and BNP, are highly elevated, but the mechanism underlying the apparent deficiency in natriuretic peptide processing is unclear. Corin is a cardiac protease that activates natriuretic peptides. In this study, we examined corin protein expression and activity in mouse and human failing hearts. Tissue samples were obtained from a mouse model of HF induced by myotrophin overexpression and from human nonfailing, hypertrophic, and failing hearts. Corin protein levels in the membrane fraction and tissue lysate were measured by Western blotting and ELISA. Corin catalytic and biological activities were measured by fluorescent substrate and pro-ANP processing assays. In mice, corin protein levels did not change with age in normal hearts but increased significantly in failing hearts. In humans, corin protein levels were similar in the atrium from nonfailing and failing hearts but were increased in the ventricle in failing hearts compared with those in nonfailing or hypertrophic hearts. Unlike the protein level, however, corin activity did not increase in failing hearts, as measured by fluorogenic substrate and pro-ANP processing assays. Our results indicate that corin activation is a rate-limiting step in failing hearts. Insufficient corin activation is expected to prevent natriuretic peptide processing and may contribute to body fluid retention and impaired cardiac function in patients with HF.