Abstract
Cardiovascular diseases (CVD) are one of the leading causes of morbidity and mortality worldwide. mtDNA (mitochondrial DNA) mutations are known to participate in the development and progression of some CVD. Moreover, specific types of mitochondria-mediated CVD have been discovered, such as MIEH (maternally inherited essential hypertension) and maternally inherited CHD (coronary heart disease). Maternally inherited mitochondrial CVD is caused by certain mutations in the mtDNA, which encode structural mitochondrial proteins and mitochondrial tRNA. In this review, we focus on recently identified mtDNA mutations associated with CVD (coronary artery disease and hypertension). Additionally, new data suggest the role of mtDNA mutations in Brugada syndrome and ischemic stroke, which before were considered only as a result of mutations in nuclear genes. Moreover, we discuss the molecular mechanisms of mtDNA involvement in the development of the disease.
Highlights
Atherosclerosis is a chronic inflammatory disease of large and medium-sized arteries that causes other dangerous complications, which are collectively defined as Cardiovascular diseases (CVD)
The application of GWAS to search for CAD risk alleles has led to the identification of new genes and many significant variants, which greatly expand our understanding of the disease, with a total of 164 chromosomal loci identified [3]
Mitochondria dysfunction is the first step in atherosclerosis development: an altered ROS level causes vascular EC dysfunction and the recruitment of circulating immune cells, initiating immune reactions for further atherosclerotic plaque formation
Summary
Atherosclerosis is a chronic inflammatory disease of large and medium-sized arteries that causes other dangerous complications, which are collectively defined as CVD (cardiovascular diseases). In addition to nuclear gene variants, mitochondrial mutations play a crucial role in many human diseases, including atherosclerosis and other CVD [5]. Mutated mitochondrial genes unbalance cellular respiration and energy production, leading to extreme ROS production, oxidative damage and mitochondria dysfunction, further triggering cellular damage, apoptosis and cell death [6]. Mitochondria dysfunction is the first step in atherosclerosis development: an altered ROS (reactive oxygen species) level causes vascular EC (endothelial cell) dysfunction and the recruitment of circulating immune cells, initiating immune reactions for further atherosclerotic plaque formation. Mutations in the nuclear genes that encode the respiratory chain subunits and proteins responsible for mtDNA maintenance (replication, transcription and copy number control), biogenesis and dynamics (fission and fusion) could cause the secondary instability of the mitochondrial genome and mitochondria dysfunction. The application of pharmacological agents to modulate mitochondrial metabolism and functions are under intensive investigation [30]
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