Remuscularization with triiodothyronine and β₁-blocker therapy reverses post-ischemic left ventricular dysfunction and adverse remodeling.

ABSTRACT: Renewal of the myocardium by preexisting cardiomyocytes is a powerful strategy for restoring the architecture and function of hearts injured by myocardial infarction. To advance this strategy, we show that combining two clinically approved drugs, but neither alone, muscularizes the heart through cardiomyocyte proliferation. Specifically, in adult murine cardiomyocytes, metoprolol, a cardioselective β₁-adrenergic receptor blocker, when given with triiodothyronine (T3, a thyroid hormone) accentuates the ability of T3 to stimulate ERK1/2 phosphorylation and proliferative signaling by inhibiting expression of the nuclear phospho-ERK1/2-specific phosphatase, dual-specificity phosphatase-5. While short-duration metoprolol plus T3 therapy generates new heart muscle in healthy mice, in

SUBMITTER: Bogush N 

PROVIDER: S-EPMC9132945 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature