HMG CoA reductase inhibition by Simvastatin gets rat β-Myosin heavy chain disappeared: A statin paradox.

""3-hydroxy-3methylglutaryl Coenzyme A reductase, the rate limiting enzyme of mevalonate pathway, generates, in addition to cholesterol, a range of prod- ucts involved in several biological functions: oligo- prenyl groups, dolichol and ubiquinone. The latter, in particular, participates in electron transport chain and, in turn, in tissue energy supply. The enzyme is inhibited by statins that, besides lowering choles- terolemia, seem to impair human energy-dependent myocardial functions (e.g. stroke volume, cardiac output, and contractile index). The modulation of heart contractile properties could be explained by the decrease of ventricle ubiquinone content and\\\/or by putative changes in proportion of the different my- osin heavy chain isoforms. Since we previously dem- onstrated that chronic statin treatment modifies my- osin heavy chain isoform pattern in skeletal muscle impairing its functional properties, this work was aimed at investigating the effects of statin chronic treatment on both ventricle ubiquinone content and myosin heavy chain isoforms. Our results showed that simvastatin treatment leads to a reduced amount of rat ventricle ubiquinone and to β myosin heavy chain disappearance. Thus, statins which are pre- scribed to prevent cardiovascular disease, might in- duce cardiac metabolic and structural modifications whose functional implications on contractility are still to be established and carefully considered.""