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

British Journal of Pharmacology
Helen KiriazisX-J Du

Abstract

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. Mice were subjected to aortic banding or sham surgery, and their cardiac function was determined by echocardiography and micromanometry. 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. 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.

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Citations

Jun 5, 2010·Current Hypertension Reports·Cheryl L Laffer, Fernando Elijovich
Jun 28, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Mingming ZhaoDaniel Bernstein
Jul 28, 2009·American Journal of Physiology. Heart and Circulatory Physiology·ByungSu YooHoward A Rockman
May 29, 2010·American Journal of Respiratory and Critical Care Medicine·Harm J BogaardNorbert F Voelkel
Oct 14, 2016·Canadian Journal of Physiology and Pharmacology·Baoling ZhuZijian Li
Jul 26, 2011·Journal of Hypertension·Peter KanellakisAlexander Bobik
Oct 11, 2013·Clinical and Experimental Pharmacology & Physiology·Hao LiYou-Yi Zhang
Jan 17, 2014·The Journal of Pharmacology and Experimental Therapeutics·Christiane NeuberAli El-Armouche
Aug 1, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yuqian ZhaoXinsheng Yao
Dec 2, 2010·Journal of Molecular and Cellular Cardiology·Brian C JensenPaul C Simpson

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