The defects in the mitochondrial genome are associated with different pathologies, including atherosclerosis. It is generally believed that atherosclerosis leads to premature cell senescence, but there is increasing evidence that cell senescence, the biomarker of which is the mutational load of mitochondrial genome, is itself a mechanistic factor of atherogenesis. The basic scientific problem addressed is an examination of functional consequences of mitochondrial DNA (mtDNA) damage based on the analysis of variability of mitochondrial genome. The paper is devoted to identification of genetic markers of mtDNA mutation burden, molecular and cellular markers of disorders in functional properties of cells arising from mutations in the mitochondrial genome, and identification of combinations of genetic markers that lead to violation of functional properties of human monocyte-macrophages. New data are presented, which resulted from whole genome sequencing of mtDNA from atherosclerotic lesions of arterial intima, the analysis of the relationship of mtDNA damage with the changes in cellular composition of arterial intima and expression of apoptosis- and inflammation-related genes, retrieving the data on mitochondrial genome variability in patients with atherosclerosis, and the study of functional activity of human blood monocytes differing substantially by the degree of mtDNA mutation burden.
Part of the book: Genetic Polymorphisms