Common genomic response in different mouse models of beta-adrenergic-induced cardiomyopathy

Article

关键词: HEART-FAILURE;    BETA(1)-ADRENERGIC RECEPTOR;    UNCOUPLING PROTEIN-2;    CARDIAC MYOCYTES;    GENE-EXPRESSION;    DOUBLE-BLIND;    OVEREXPRESSION;    CARVEDILOL;    BLOCKADE;    FAMILY;   

DOI  :  10.1161/01.CIR.0000101922.18151.7B

来源: SCIE

【 摘 要 】

Background-Although beta-adrenergic receptor (AR) blockade therapy is beneficial in the treatment of heart failure, little is known regarding the transcriptional mechanisms underlying this salutary action. Methods and Results-In the present study, we screened mice overexpressing Gsalpha, beta(1)AR, beta(2)AR, or protein kinase A to test if a common genomic pathway exists in different models with enhanced beta-adrenergic signaling. In mice overexpressing Gsalpha, differentially expressed genes were identified by mRNA profiling. In addition to well-known markers of cardiac hypertrophy (atrial natriuretic factor, CARP, and beta-myosin heavy chain), uncoupling protein 2 (UCP2), a protein involved in the control of mitochondrial membrane potential, and four-and-a-half LIM domain protein-1 (FHL1), a member of the LIM protein family, were predicted to be upregulated. Upregulation of these genes was confirmed by quantitative reverse transcriptase-polymerase chain reaction at all time points tested during the development of cardiomyopathy in mice overexpressing Gsalpha. In mice overexpressing beta(1)AR, beta(2)AR, or protein kinase A, increased UCP2 and FHL1 expression was also observed at the onset of cardiomyopathy. betaAR blockade treatment reversed the cardiomyopathy and suppressed the increased expression of UCP2 and FHL1 in mice overexpressing Gsalpha. Conclusions-UCP2 and FHL1 are important candidate genes that correlate with the development of betaAR-induced cardiomyopathy in different mouse models with enhanced betaAR signaling. In addition to preserving cardiac function, betaAR blockade treatment also prevents the genomic regulation that correlates with the onset of heart failure.

【 授权许可】

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