Depressed Corin Levels Indicate Early Systolic Dysfunction Before Increases of Atrial Natriuretic Peptide/B-Type Natriuretic Peptide and Heart Failure Development.
Depressed Corin Levels Indicate Early Systolic Dysfunction Before Increases of Atrial Natriuretic Peptide/B-Type Natriuretic Peptide and Heart Failure Development.
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DOI：
10.1161/hypertensionaha.115.06300
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发表时间：
2016-02
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：
Tripathi R;Wang D;Sullivan R;Fan TH;Gladysheva IP;Reed GL
Dilated cardiomyopathy is a major cause of heart failure that affects millions. Corin cleaves and biologically activates pro-atrial natriuretic peptide (pro-ANP) and pro-B-type natriuretic peptide (pro-BNP). High corin levels reduce the development of systolic dysfunction and heart failure in experimental dilated cardiomyopathy. Yet, patients with significant heart failure unexpectedly show low corin levels with high plasma ANP/BNP levels. Therefore, we examined the relationship between cardiac corin expression, ANP/BNP levels and the stages of heart failure. We used a well-established, dilated cardiomyopathy model to evaluate gene and protein expression as mice longitudinally developed Stages A-D heart failure. Cardiac systolic function (ejection fraction) continuously declined over time (P<0.001). Cardiac corin transcripts were decreased at early Stage B heart failure and remained low through Stages C-D (P<0.001). Cardiac corin levels were positively correlated with systolic function (r=0.96, P=0.003) and inversely with lung water (r=-0.92, P=0.001). In contrast, cardiac pro-ANP/BNP transcripts increased later (Stage C-D) and plasma levels rose only with terminal heart failure (Stage D, P<0.001). Immunoreactive plasma ANP and BNP levels were positively associated with plasma cyclic guanosine monophosphate (cGMP) levels (r=0.82, P=0.01 & r=0.8, P=0.02 respectively). In experimental dilated cardiomyopathy, corin levels declined early with progressive systolic dysfunction before the development of heart failure, while significant increases in plasma ANP, BNP and cGMP levels were found only in later Stage (C, D) heart failure. This dyssynchrony in expression of corin vs. ANP/BNP may impair cleavage-activation of pro-natriuretic peptides and thereby promote the transition from earlier to later stage heart failure.
