Knockout of beta(1)- and beta(2)-adrenoceptors attenuates pressure overload-induced cardiac hypertrophy and fibrosis.

Abstract

BACKGROUND AND PURPOSE The role of beta-adrenoceptors in heart disease remains controversial. Although beta-blockers ameliorate the progression of heart disease, the mechanism remains undefined. We investigated the effect of beta-adrenoceptors on cardiac hypertrophic growth using beta(1)- and beta(2)-adrenoreceptor knockout and wild-type (WT) mice. EXPERIMENTAL APPROACH Mice were subjected to aortic banding or sham surgery, and their cardiac function was determined by echocardiography and micromanometry. KEY RESULTS At 4 and 12 weeks after aortic banding, the left ventricle:body mass ratio was increased by 80-87% in wild-type mice, but only by 15% in knockouts, relative to sham-operated groups. Despite the blunted hypertrophic growth, ventricular function in knockouts was maintained. WT mice responded to pressure overload with up-regulation of gene expression of inflammatory cytokines and fibrogenic growth factors, and with severe cardiac fibrosis. All these effects were absent in the knockout animals. CONCLUSION AND IMPLICATIONS Our findings of a markedly attenuated cardiac hypertrophy and fibrosis following pressure overload in this knockout model emphasize that beta-adrenoceptor signalling plays a central role in cardiac hypertrophy and maladaptation following pressure overload.

DOI: 10.1038/sj.bjp.0707622
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@article{Kiriazis2008KnockoutOB, title={Knockout of beta(1)- and beta(2)-adrenoceptors attenuates pressure overload-induced cardiac hypertrophy and fibrosis.}, author={Helen Kiriazis and K Wang and Qing Xu and X. M. Gao and Ziqui Ming and Y Su and X-L Moore and Gavin W . Lambert and Marie E. Gibbs and Anthony Michael Dart and Xiao-jun Du}, journal={British journal of pharmacology}, year={2008}, volume={153 4}, pages={684-92} }