Downregulation of beta-Adrenoceptors in Isoproterenol-Induced Cardiac Remodeling through HuR

beta-adrenergic receptors (beta-ARs) play an important role in cardiac remodeling, which is the key pathological process in various heart diseases and leads to heart failure. However, the regulation of beta-AR expression in remodeling hearts is still unclear. This study aims to clarify the possible mechanisms underlying the regulation of beta(1)- and beta(2)-AR expression in cardiac remodeling. The rat model of cardiac remodeling was established by subcutaneous injection of isoproterenol(ISO) at the dose of 0.25 mg.kg(-1).d(-1) for 7days. We found that the expression of beta(1)-and beta(2)-ARs decreased in the remodeling heart. The mechanisms may include the inhibition of DNA transcription and the increase of mRNA degradation. cAMPresponse element binding protein(CREB) is a well-known transcription factor of beta-AR. However, the expression and activation of CREB was not changed in the remodeling heart. Further, human Antigen-R (HuR), a RNA binding protein, which binds to the 3'-untranslated region of the beta-AR mRNA and promotes RNA degradation, was increased in the remodeling model. And in vitro, HuR deficiency reversed the reduction of beta-AR mRNA induced by ISO. Therefore, the present findings indicate that HuR, but not CREB, is responsible for the reduction of beta-AR expression in ISO induced cardiac remodeling.National Basic Research Program of China [2014CBA02000]; National Natural Science Foundation of China [81270157, 81471893, 91539123, 81070078]; National key Scientific Instrument and Equipment Development Project of China [2013YQ170525]SCI(E)PubMedARTICLEzhengxp001@mail.xjtu.edu.cn; lizijian@bjmu.edu.cn4e01520051