Faculty Collaboration Database

Alpha-calcitonin gene-related peptide is protective against pressure overload-induced heart failure. Regul Pept 2013 Aug 10;185:20-8

Date

07/03/2013

Pubmed ID

23816470

DOI

10.1016/j.regpep.2013.06.008

Scopus ID

2-s2.0-84880382014 (requires institutional sign-in at Scopus site)   41 Citations

Abstract

The sensory neuropeptide, α-calcitonin gene-related peptide (α-CGRP) is protective against hypertension-induced heart damage and cardiac ischemia/reperfusion injury. To determine whether this neuropeptide is also cardioprotective in heart failure, this study examined whether the absence of α-CGRP exacerbated the adverse cardiac remodeling, dysfunction and mortality in pressure overload heart failure induced by transverse aortic constriction (TAC). Male α-CGRP knockout (KO) and wild type (WT) mice had TAC or sham surgery at day 0 and were studied on days 3, 14, 21, and 28. The survival rate of TAC α-CGRP KO mice was lower than the TAC WT mice over the duration of the protocol. Left ventricular α-CGRP content in TAC WT mice was higher at days 3, 14, and 21 than sham WT mice. Echocardiography demonstrated greater adverse cardiac remodeling and dysfunction in the TAC α-CGRP KO compared to the TAC WT mice. The lung/body weight ratios and left ventricular masses were higher in TAC α-CGRP KO compared to the TAC WT mice. While there was increased cardiac fibrosis in the TAC WT mice compared to shams, the TAC α-CGRP KO mice had markedly increased fibrosis above that of the TAC WT mice. TAC WT mice had greater cardiac inflammation, cell death, and adaptive angiogenesis compared to sham mice. Importantly, the TAC α-CGRP KO mice had greater inflammation, cell death, and attenuation of angiogenesis compared to TAC WT hearts. Thus, α-CGRP plays a significant protective role in TAC-induced heart failure which may be mediated by decreased inflammation, cell death, and fibrosis.

Author List

Li J, Levick SP, DiPette DJ, Janicki JS, Supowit SC

MESH terms used to index this publication - Major topics in bold

Angiogenic Proteins
Animals
Apoptosis
Calcitonin Gene-Related Peptide
Coronary Vessels
Fibrosis
Heart Failure
Heart Ventricles
Hypertension
Lung
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Microvessels
Myocardium
Myocytes, Cardiac
Necrosis
Neovascularization, Physiologic
Organ Size
Ultrasonography
Ventricular Remodeling