The role of alterations of mitochondrial DNA (mtDNA) in the development of human pathologies is not understood well. Most of mitochondrial mutations are characterized by the phenomenon of heteroplasmy which is defined as the presence of a mixture of more than one type of an organellar genome within a cell or tissue. The level of heteroplasmy varies in wide range, and the expression of disease is dependent on the percent of alleles bearing mutations, thus allowing consumption that an upper threshold level may exist beyond which the mitochondrial function collapses. Recent findings have demonstrated that some mtDNA heteroplasmic mutations are associated with widely spread chronic diseases, including atherosclerosis and cancer. Actually, each etiological mtDNA mutation has its own heteroplasmy threshold that needs to be measured. Therefore, quantitative evaluation of a mutant allele of mitochondrial genome is an obvious methodological challenge, since it may be a keystone for diagnostics of individual genetic predisposition to the disease. This review provides a comprehensive comparison of methods applicable to the measurement of heteroplasmy level of mitochondrial mutations associated with the development of pathology, in particular, in atherosclerosis and its clinical manifestations.

Atherosclerosis, the primary cause of cardiovascular disease, is a complex and multifactorial pathology resulted from the harmful interactions between genetic and environmental factors. There is a growing body of evidence in support of the 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) damage may be directly involved in the development of multiple mechanisms of atherogenesis. Recent findings show that several heteroplasmic mutations of mtDNA are related to atherosclerosis, coronary heart disease and several atherosclerosis-related diseases such as arterial hypertension and diabetes mellitus. Therefore, heteroplasmic mtDNA mutations could represent a promising molecular biomarker of genetic susceptibility to atherosclerosis and related pathologies. This review is focused on the latest findings in the studies of mutations of mitochondrial genome, which are associated with atherosclerosis and atherosclerosis- related diseases.

No abstract

No abstract

No abstract