Mitochondrion as a Selective Target for the Treatment of Atherosclerosis: Role of Mitochondrial DNA Mutations and Defective Mitophagy in the Pathogenesis of Atherosclerosis and Chronic Inflammation

• Published in: Current neuropharmacology 2020-01, Vol.18 (11), p.1064-1075
• Main Authors: Orekhov, Alexander N, Poznyak, Anastasia V, Sobenin, Igor A, Nikifirov, Nikita N, Ivanova, Ekaterina A
• Format: Article
• Language: English
• ISSN: 1570-159X; 1875-6190
• DOI: 10.2174/1570159X17666191118125018

Background: Atherosclerosis is a chronic inflammatory condition that affects different arteries in the human body and often leads to severe neurological complications, such as stroke and its sequelae. Affected blood vessels develop atherosclerotic lesions in the form of focal thickening of the intimal layer, so called atherosclerotic plaques. Objectives: Despite the high priority of atherosclerosis research for global health and the numerous preclinical and clinical studies conducted, currently, there is no effective pharmacological treatment that directly impacts atherosclerotic plaques. Many knowledge gaps exist in our understanding of the mechanisms of plaque formation. In this review, we discuss the role of mitochondria in different cell types involved in atherogenesis and provide information about mtDNA mutations associated with the disease. Results: Mitochondria of blood and arterial wall cells appear to be one of the important factors in disease initiation and development. Significant experimental evidence connects oxidative stress associated with mitochondrial dysfunction and vascular disease. Moreover, mitochondrial DNA (mtDNA) deletions and mutations are being considered as potential disease markers. Further study of mtDNA damage and associated dysfunction may open new perspectives for atherosclerosis treatment. Conclusion: Mitochondria can be considered as important disease-modifying factors in several chronic pathologies. Deletions and mutations of mtDNA may be used as potential disease markers. Mitochondria-targeting antioxidant therapies appear to be promising for the development of treatment of atherosclerosis and other diseases associated with oxidative stress and chronic inflammation.