title: Depressed Corin Levels Indicate Early Systolic Dysfunction Before Increases of Atrial Natriuretic Peptide/B-Type Natriuretic Peptide and Heart Failure Development.
abstract: Dilated cardiomyopathy is a major cause of heart failure (HF) 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 HF in experimental dilated cardiomyopathy. Yet, patients with significant HF 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 HF. We used a well-established, dilated cardiomyopathy model to evaluate gene and protein expression as mice longitudinally developed Stages A-D HF. Cardiac systolic function (ejection fraction) continuously declined over time (P<0.001). Cardiac corin transcripts were decreased at early Stage B HF and remained low through Stages C and 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 (Stages C and D) and plasma levels rose only with terminal HF (Stage D, P<0.001). Immunoreactive plasma ANP and BNP levels were positively associated with plasma cyclic guanosine monophosphate levels (r=0.82, P=0.01 and r=0.8, P=0.02, respectively). In experimental dilated cardiomyopathy, corin levels declined early with progressive systolic dysfunction before the development of HF, whereas significant increases in plasma ANP, BNP, and cyclic guanosine monophosphate levels were found only in later stage (C and D) HF. This dyssynchrony in expression of corin versus ANP/BNP may impair cleavage activation of pro-natriuretic peptides, and thereby promote the transition from earlier to later stage HF.
authors.affiliation: From the Departments of Medicine (R.T., D.W., T.-H.M.F., I.P.G., G.L.R.) and Comparative Medicine (R.S.), University of Tennessee Health Science Center, Memphis.
authors.forename: Ranjana
authors.initials: R
authors.lastname: Tripathi
authors.affiliation: From the Departments of Medicine (R.T., D.W., T.-H.M.F., I.P.G., G.L.R.) and Comparative Medicine (R.S.), University of Tennessee Health Science Center, Memphis.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: From the Departments of Medicine (R.T., D.W., T.-H.M.F., I.P.G., G.L.R.) and Comparative Medicine (R.S.), University of Tennessee Health Science Center, Memphis.
authors.forename: Ryan
authors.initials: R
authors.lastname: Sullivan
authors.affiliation: From the Departments of Medicine (R.T., D.W., T.-H.M.F., I.P.G., G.L.R.) and Comparative Medicine (R.S.), University of Tennessee Health Science Center, Memphis.
authors.forename: Tai-Hwang M
authors.initials: TH
authors.lastname: Fan
authors.affiliation: From the Departments of Medicine (R.T., D.W., T.-H.M.F., I.P.G., G.L.R.) and Comparative Medicine (R.S.), University of Tennessee Health Science Center, Memphis. igladysh@uthsc.edu glreed@uthsc.edu.
authors.forename: Inna P
authors.initials: IP
authors.lastname: Gladysheva
authors.affiliation: From the Departments of Medicine (R.T., D.W., T.-H.M.F., I.P.G., G.L.R.) and Comparative Medicine (R.S.), University of Tennessee Health Science Center, Memphis. igladysh@uthsc.edu glreed@uthsc.edu.
authors.forename: Guy L
authors.initials: GL
authors.lastname: Reed
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism*; D013599:Systole; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; C485617:Corin protein, mouse; D012697:Serine Endopeptidases
keywords: atrial natriuretic peptide; corin protein; dilated cardiomyopathy; heart failure; natriuretic peptides