Regulation of Human Cardiac Myosin Heavy Chain Gene Expression by Thyroid Hormone

Abstract

Rat cardiac myosin heavy chain (MHC) genes are regulated in ventricular myocardium by 3,5,3′-triiodo-L-thyronine (T₃), which stimulates expression of the α-MHC gene and decreases β-MHC mRNA production (1,2). The protein products of the cardiac MHC genes combine to produce three heavy chain isoforms, V₁(α,α), V₂(α,β), and V₃(β,β), in order of decreasing electrophoretic mobility and Ca²⁺-ATPase activity (3). The relative proportions of these isoforms may be functionally important because the speed of contraction in both cardiac and skeletal muscles has been shown to be related to myosin ATPase (4). Recently, some forms of familial hypertrophic cardiomyopathy have been reported to be linked directly to either a partial duplication of the cardiac MHC genes or to a missense mutation of the β-MHC gene (5,6)