Therapeutic effect of β-adrenoceptor blockers using a mouse model of dilated cardiomyopathy with a troponin mutation

Dong Yun Zhan, Sachio Morimoto, Cheng Kun Du, Yuan Yuan Wang, Qun Wei Lu, Atsushi Tanaka, Tomomi Ide, Yoshikazu Miwa, Fumi Takahashi-Yanaga, Toshiyuki Sasaguri

研究成果: ジャーナルへの寄稿学術誌査読

26 被引用数 (Scopus)

抄録

AimsExtensive clinical studies have demonstrated that β-adrenoceptor blocking agents (β-blockers) are beneficial in the treatment of chronic heart failure, which is due to various aetiologies, including idiopathic dilated cardiomyopathy (DCM) and ischaemic heart disease. However, little is known about the therapeutic efficacy of β-blockers in the treatment of the inherited form of DCM, of which causative mutations have recently been identified in various genes, including those encoding cardiac sarcomeric proteins. Using a mouse model of inherited DCM with a troponin mutation, we aim to study the treatment benefits of β-blockers.Methods and resultsThree different types of β-blockers, carvedilol, metoprolol, and atenolol, were orally administered to a knock-in mouse model of inherited DCM with a deletion mutation ΔK210 in the cardiac troponin T gene (TNNT2). Therapeutic effects were examined on the basis of survival and myocardial remodelling. The lipophilic β1-selective β-blocker metoprolol was found to prevent cardiac dysfunction and remodelling and extend the survival of knock-in mice. Conversely, both the non-selective β-blocker carvedilol and the hydrophilic β1-selective β-blocker atenolol had no beneficial effects on survival and myocardial remodelling in this mouse model of inherited DCM.ConclusionThe highly lipophilic β1-selective β-blocker metoprolol, known to prevent ventricular fibrillation via central nervous system-mediated vagal activation, may be especially beneficial to DCM patients showing a family history of frequent sudden cardiac death, such as those with a deletion mutation ΔK210 in the TNNT2 gene.

本文言語英語
ページ(範囲)64-71
ページ数8
ジャーナルCardiovascular research
84
1
DOI
出版ステータス出版済み - 10月 2009

!!!All Science Journal Classification (ASJC) codes

  • 医学一般

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