Corin overexpression improves cardiac function, heart failure, and survival in mice with dilated cardiomyopathy.
Corin overexpression improves cardiac function, heart failure, and survival in mice with dilated cardiomyopathy.
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DOI：
10.1161/hypertensionaha.112.193631
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发表时间：
2013-02
期刊：
影响因子：
--
通讯作者：
Reed GL
中科院分区：
文献类型：
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作者：
Gladysheva IP;Wang D;McNamee RA;Houng AK;Mohamad AA;Fan TM;Reed GL
由扩张型心肌病和其他心脏疾病如高血压引起的心力衰竭是一个主要的公共卫生问题，具有高发病率和死亡率。Corin是一种切割利钠肽的心肌酶，是心肌病和心力衰竭的一种有前途的生物标志物，但其在这些过程中的功能作用尚不清楚。我们评估了corin在具有良好特征的扩张型心肌病模型小鼠中的潜在作用。扩张型心肌病小鼠在corin低表达的情况下发生心力衰竭、收缩功能降低、心脏纤维化和死亡率加速。在野生型小鼠中，转基因、心脏靶向、corin过度表达增强了环磷酸鸟苷和对心房利钠肽原的血压反应，但不影响心脏大小、收缩力、体重、存活率和血压。在扩张型心肌病小鼠中，corin过表达显著减少心肌纤维化的发展（p<0.05）。Corin过表达还增强心脏收缩功能（缩短分数和射血分数（p<0.01）），并且其显著减少心力衰竭，如通过肺水（p<0.05）和肺泡充血（p<0.001）评估的。与这些观察结果一致，corin过表达显著延长了扩张型心肌病小鼠的寿命（p<0.0001）。这些结果提供了第一个实验证据，corin表达通过调节心肌纤维化、心功能、心力衰竭和存活在心肌病中起作用。
Heart failure, caused by dilated cardiomyopathy and other cardiac disorders such as hypertension, is a major public health problem with high morbidity and mortality. Corin, a cardiac enzyme that cleaves natriuretic peptides, is a promising biomarker of cardiomyopathy and heart failure—but its functional role in these processes is not understood. We evaluated the potential effects of corin in mice with a well-characterized model of dilated cardiomyopathy. Mice with dilated cardiomyopathy developed heart failure, reduced contractile function, cardiac fibrosis and accelerated mortality in the setting of low corin expression. In wild-type mice, transgenic, cardiac-targeted, over-expression of corin enhanced cyclic guanosine monophosphate and blood pressure responses to pro-atrial natriuretic peptide, but did not affect heart size, contractility, body weights, survival and blood pressure. In mice with dilated cardiomyopathy, corin overexpression significantly reduced the development of myocardial fibrosis (p<0.05). Corin over-expression also enhanced heart contractile function (fractional shortening and ejection fraction (p<0.01) and it significantly reduced heart failure as assessed by lung water (p<0.05) and alveolar congestion (p<0.001). Consistent with these observations, corin over-expression significantly prolonged life in mice with dilated cardiomyopathy (p<0.0001). These results provide the first experimental evidence that corin expression plays a role in cardiomyopathy by modulating myocardial fibrosis, cardiac function, heart failure and survival.