Mitochondrial Mutations in Atherosclerosis: New Solutions in Research and Possible Clinical Applications

Igor   A.   Sobenin; Dimitry   A.   Chistiakov; Yuri   V.   Bobryshev; Anton   Y.   Postnov; Alexander   N.   Orekhov

doi:10.2174/1381612811319330013

Abstract

Cardiovascular diseases are the leading causes of morbidity and mortality in many industrialized societies. Atherosclerosis is the major risk factor for the development of cardiovascular disease based on arterial endothelial dysfunction caused by the impairment of endothelial-dependent dilation. Atherosclerosis is a complex vascular disease resulted from the harmful interactions between genetic and environmental factors. There is a growing body of evidence in support of a non-redundant role of mitochondrial factors in the pathogenesis of atherosclerosis. Impaired mitochondrial function and structural and qualitative changes in mitochondrial components such as mitochondrial DNA (mtDNA) may be directly involved in the development of multiple atherogenic mechanisms including advanced oxidative stress, abnormalities in glucose and fat metabolism, and altered energy homeostasis. Recent findings showed that the heteroplasmy level of some somatic mtDNA is associated with coronary atherosclerosis. Although this field should further widely elaborated, heteroplasmic mtDNA mutations could represent a new promising molecular biomarker of genetic susceptibility to atherosclerosis and related pathologic conditions. In this review, we critically consider the contribution of mitochondria-related factors to the pathogenesis of the arterial vascular pathology.

Keywords: Atherosclerosis, atherogenesis, mitochondrial DNA, mutations, heteroplasmy, mitochondrial dysfunction, oxidative stress, cell functions.