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.