Plasma Corin as a Predictor of Cardiovascular Events in Patients With Chronic Heart Failure

Zhou, Xiang; Chen, Jian-Chang; Liu, Ying; Yang, Hui; Du, Kang; Kong, Yuan; Xu, Xiaohua

doi:10.1016/j.jchf.2016.03.006

Cited by 39 publications

(37 citation statements)

References 20 publications

(6 reference statements)

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“…Spatially, corin was reduced in the infarct area and the ischemic border zone, when compared to areas remote from the ischemic zone, as demonstrated by specific immunostaining. Prior studies showed both plasma and cardiac corin levels were lower in chronic heart failure patients and experimental heart failure models [ 4 , 7 – 10 , 15 , 27 ] and the trend of changes in plasma and cardiac corin levels was consistent. Given the marked decline in cardiac corin expression, the possible reason for increases in plasma corin levels appear to be enhanced release of corin from ischemic or infarcted myocytes.…”

Section: Discussionsupporting

confidence: 53%

Increases in plasma corin levels following experimental myocardial infarction reflect the severity of ischemic injury

et al. 2018

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Following acute myocardial infarction, clinical studies show alterations in the blood levels of corin, a cardiac-selective activator of the natriuretic peptides pro-atrial natriuretic peptide (pro-ANP) and pro-B-type natriuretic peptide (pro-BNP). However, the temporal changes in circulating and cardiac corin levels and their relationships to the severity of myocardial infarction have not been studied. The main objective of this study was to examine the relationship between cardiac and circulating corin levels and their association with cardiac systolic function and infarct size during the early phase of acute myocardial infarction (<72 h) in a translationally relevant induced coronary ligation mouse model. This acute phase timeline was chosen to correlate with the clinical practice within which blood samples are collected from myocardial infarction patients. Heart and plasma samples were examined at 3, 24, and 72 hours post acute myocardial infarction. Plasma corin levels were examined by enzyme-linked immunosorbent assay, transcripts of cardiac corin, pro-ANP and pro-BNP by quantitative real-time polymerase chain reaction, cardiac corin expression by immunohistology, infarct size by histology and heart function by echocardiography. Plasma corin levels were significantly increased at 3 (P<0.05), 24 (P<0.001), and 72 hours (P<0.01) post-acute myocardial infarction. In contrast, cardiac corin transcript levels dropped by 5% (P>0.05), 69% (P<0.001) and 65% (P<0.001) and immunoreactive cardiac corin protein levels dropped by 30% (P<0.05), 76% (P<0.001) and 75% (P<0.001), while cardiac pro-ANP and pro-BNP transcript levels showed an opposite pattern. Plasma corin levels were negatively correlated with immunoreactive cardiac corin (P<0.01), ejection fraction (P<0.05) and fractional shortening (P<0.05), but positively correlated with infarct size (P<0.01). In conclusion, acute myocardial infarction induces rapid increases in plasma corin and decreases in cardiac corin levels. In the early phase of acute myocardial infarction, plasma corin levels are inversely correlated with heart function and may reflect the severity of myocardial damage.

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Section: Discussionsupporting

confidence: 53%

Increases in plasma corin levels following experimental myocardial infarction reflect the severity of ischemic injury

et al. 2018

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“…Converging lines of evidence from clinical and translational studies have shown that genetic abnormalities and reduction in corin cardiac expression level negatively affect DCM and HFrEF outcomes. Cardiac transcripts and circulating levels of corin are depressed in patients and translational animal models with DCM and HFrEF [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]35,36,51], and are pathologically modulated in DCM before the onset of edema and other clinical signs and symptoms of HFrEF [22,23]. In a translationally relevant mouse model of DCM-HFrEF with reduced cardiac and plasma corin levels, we reported that genetic restoration of cardiac-specific catalytically active, native corin improved systolic function, reduced myocardial fibrosis, decreased edema, and prolonged survival [16,17].…”

Section: Discussionmentioning

confidence: 99%

“…A growing body of evidence in humans and experimental models suggests that corin, a cardiac transmembrane II serine protease, plays diagnostic, prognostic, and protective roles in DCM and HFrEF development [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. Cardiac corin is co-expressed with pro-atrial natriuretic peptide (pro-ANP) and localized on the cardiomyocyte surface [25,26], where it cleaves/activates secreted pro-ANP generating biologically active ANP peptides.…”

Section: Introductionmentioning

confidence: 99%

Cardiac-Specific Overexpression of Catalytically Inactive Corin Reduces Edema, Contractile Dysfunction, and Death in Mice with Dilated Cardiomyopathy

Tripathi

Sullivan

Fan

et al. 2019

IJMS

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Humans with dilated cardiomyopathy (DCM) and heart failure (HF) develop low levels of corin, a multi-domain, cardiac-selective serine protease involved in natriuretic peptide cleavage and sodium and water regulation. However, experimental restoration of corin levels markedly attenuates HF progression. To determine whether the beneficial effects of corin in HF require catalytic activity, we engineered cardiac overexpression of an enzymatically inactive corin transgene (corin-Tg(i)). On a wild-type (WT) background, corin-Tg(i) had no evident phenotypic effects. However, in a well-established genetic model of DCM, corin-Tg(i)/DCM mice had increased survival (p < 0.01 to 0.001) vs. littermate corin-WT/DCM controls. Pleural effusion (p < 0.01), lung edema (p < 0.05), systemic extracellular free water (p < 0.01), and heart weight were decreased (p < 0.01) in corin-Tg(i)/DCM vs. corin-WT/DCM mice. Cardiac ejection fraction and fractional shortening improved (p < 0.01), while ventricular dilation decreased (p < 0.0001) in corin-Tg(i)/DCM mice. Plasma atrial natriuretic peptide, cyclic guanosine monophosphate, and neprilysin were significantly decreased. Cardiac phosphorylated glycogen synthase kinase-3β (pSer9-GSK3β) levels were increased in corin(i)-Tg/DCM mice (p < 0.01). In summary, catalytically inactive corin-Tg(i) decreased fluid retention, improved contractile function, decreased HF biomarkers, and diminished cardiac GSK3β activity. Thus, the protective effects of cardiac corin on HF progression and survival in experimental DCM do not require the serine protease activity of the molecule.

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“…In African Americans, for example, a corin variant with reduced pro‐ANP processing activity is associated with hypertension and cardiac hypertrophy (Dries et al., ; Rame et al., ). More recently, low plasma or serum corin levels have been reported in patients with heart failure (Dong et al., ; Ibebuogu, Gladysheva, Houng, & Reed, ; Zhou et al., ), coronary artery disease (Barnet et al., ; Peleg, Ghanim, Vered, & Hasin, ), myocardial infarction (Zhang et al., ; Zhou et al., ), and stroke (Hu et al., ; Peng et al., ), suggesting that corin deficiency may contribute to major cardiovascular diseases.…”

Section: Introductionmentioning

confidence: 99%

Identification and functional analysis ofCORINvariants in hypertensive patients

et al. 2017

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Corin is a serine protease that activates atrial natriuretic peptide (ANP). CORIN gene variants have been reported in patients with hypertension. To date, however, the prevalence of CORIN variants in hypertensive patients remains unknown. To understand the prevalence and functional significance of CORIN variants in hypertension, we sequenced CORIN exons in 300 normal and 401 hypertensive individuals in a Chinese population and identified nine nonsynonymous variants, of which eight were not characterized previously. Among them, variants c.131A > G (p.Tyr13Cys), c.376G > T (p.Asp95Tyr), c.1094T > G (p.Leu334Trp), and c.1667G > A (p.Arg525His) occurred similarly in both normal and hypertensive individuals. Variants c1139G > A (p.Arg349His), c.2689C > T (p.Pro866Ser), and c.2864C > T (p.Thr924Met) were found once each in hypertensive individuals. Variant c.1683G > T (p.Arg530Ser) occurred preferentially in hypertensive individuals [10/401 (2.5%) vs. 1/300 (0.3%) in normal individuals; P = 0.023], which was confirmed in another independent cohort [9/368 (2.44%) in hypertensive and 2/377 (0.53%) in normal individuals; P = 0.033]. In biochemical and cell-based functional studies, variants p.Arg530Ser and p.Thr924Met, but not p.Tyr13Cys, p.Asp95Tyr, p.Leu334Trp, p.Arg349His, p.Arg525His, and p.Pro866Ser, exhibited reduced pro-ANP processing activity, which was caused by endoplasmic reticulum retention and poor zymogen activation, respectively. These results indicate that genetic variants impairing corin function are not uncommon in general populations and that such variants may be an important contributing factor in hypertension.

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Plasma Corin as a Predictor of Cardiovascular Events in Patients With Chronic Heart Failure

Abstract: Our study demonstrates that plasma corin is a valuable prognostic marker of MACE in patients with CHF, independent of established conventional risk factors.

Cited by 39 publications

References 20 publications

Increases in plasma corin levels following experimental myocardial infarction reflect the severity of ischemic injury

Increases in plasma corin levels following experimental myocardial infarction reflect the severity of ischemic injury

Cardiac-Specific Overexpression of Catalytically Inactive Corin Reduces Edema, Contractile Dysfunction, and Death in Mice with Dilated Cardiomyopathy

Identification and functional analysis ofCORINvariants in hypertensive patients

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