TITLE:
HMG CoA reductase inhibition by Simvastatin gets rat β-Myosin heavy chain disappeared: A statin paradox
AUTHORS:
Laura Trapani, Marco Segatto, Adam Jozwiak, Ewa Swiezewska, Valentina Pallottini
KEYWORDS:
Heart; Myosin Heavy Chains; Statins; Ubiquinone
JOURNAL NAME:
Open Journal of Molecular and Integrative Physiology,
Vol.3 No.1,
February
18,
2013
ABSTRACT: 3-hydroxy-3methylglutaryl
Coenzyme A reductase, the rate limiting enzyme of mevalonate pathway,
generates, in addition to cholesterol, a range of products involved in
several biological functions: oligoprenyl 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 cholesterolemia, 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 myosin heavy chain isoforms. Since we previously demonstrated that chronic
statin treatment modifies myosin 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 prescribed to
prevent cardiovascular disease, might induce cardiac metabolic and structural
modifications whose functional implications on contractility are still to be
established and carefully considered.