Heart Failure

Ngo, D.; Horowitz, John D.; Sverdlov, Aaron L.

doi:10.1161/hypertensionaha.112.196253

Cited by 15 publications

(11 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…9, 10 Thus, it is reasonable to hypothesize that corin and the pro-NPs are coordinately regulated to forestall the development of HF as systolic function declines. 7, 11 However, when measured at single time points during overt systolic HF in humans 12–15 and in mice, 9, 17 cardiac and plasma levels of corin were diminished and ANP/BNP were paradoxically increased. In this study we examined the longitudinal relationship between corin and NP expression as systolic dysfunction progressed in DCM.…”

Section: Discussionmentioning

confidence: 99%

“…A pattern of low corin and high ANP, BNP blood levels has been noted at single time points in patients admitted for treatment of acute systolic HF. 12, 13, 15 Although coordinate regulation of pro-ANP/pro-BNP and corin genes by GATA-4 and other transcription factors has been predicted for hypertrophic conditions, 11, 23 recent studies of systolic and diastolic overload show a divergence in the expression of these genes. 24 …”

Section: Discussionmentioning

confidence: 99%

“…31 This may contribute to the decreased cleavage of pro-NPs reported in human HF 13, 15, 25 lending support to the idea that HF is “a corin-deficient state” in which low corin levels may have a causative role. 11 Still, the mechanisms responsible for the dyssynchronous regulation of corin and the NPs are unknown. It will be important to determine how dyssynchronous expression of the NP system affects the activity of the renin angiotensin aldosterone system which also modulates HF in DCM.…”

Section: Discussionmentioning

confidence: 99%

“…9 Recent experimental data shows that ANP also prevents HF and the progression of experimental DCM. 10 While the components of the corin-NPs-NPRA pathway appear to protect against experimental HF 7 , recent data suggest that this pathway is dysregulated in overt HF 9, 11, 12 . Levels of circulating immunoreactive ANP and BNP rise, 2, 3, 5 while circulating levels of corin unexpectedly are depressed in patients with severe HF.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Depressed Corin Levels Indicate Early Systolic Dysfunction Before Increases of Atrial Natriuretic Peptide/B-Type Natriuretic Peptide and Heart Failure Development

et al. 2016

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Depressed Corin Levels Indicate Early Systolic Dysfunction Before Increases of Atrial Natriuretic Peptide/B-Type Natriuretic Peptide and Heart Failure Development

et al. 2016

View full text Add to dashboard Cite

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

Neprilysin Inhibition in Heart Failure with Reduced Ejection Fraction: A Clinical Review

et al. 2015

View full text Add to dashboard Cite

There has been a 10-year hiatus in the approval of a new pharmacotherapy for patients with chronic heart failure with a reduced ejection fraction (HFrEF). Combining an angiotensin receptor blocker, valsartan, with sacubitril, an inhibitor of neprilysin, results in increasing levels of natriuretic peptides that counterbalance high circulating levels of neurohormones in HFrEF. This has resulted in the development of a new agent, LCZ696. A comprehensive overview of LCZ696, its pharmacology, its role in the pathophysiology of HFrEF, completed and future clinical trial information, specific critical issues, and the place of LCZ696 in HFrEF therapy are presented.

show abstract

Heart Failure

Cited by 15 publications

References 12 publications

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

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

Neprilysin Inhibition in Heart Failure with Reduced Ejection Fraction: A Clinical Review

Contact Info

Product

Resources

About