Genetics of Arterial-Wall-Specific Mechanisms in Atherosclerosis: Focus on Mitochondrial Mutations

Orekhov, Alexander N.; Ivanova, Ekaterina A.; Markin, Alexander M.; Nikiforov, Nikita G.; Собенин, И.А.

doi:10.1007/s11883-020-00873-5

Cited by 9 publications

(4 citation statements)

References 82 publications

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“…20 The development and formation of atherosclerotic plaques involve a variety of mechanisms that direct the role of resident and recruited cell types, including endothelial cells (ECs), VSMCs, and monocyte/ macrophages (Mu). 21 Recent studies have shown that mitophagy in ECs, VSMCs, and Mu is essential to maintain plaque stability during the development of AS. 22,23 Focusing on mitophagy as a starting point in this disease state has become a topic of intense research interest in recent years.…”

Section: Mitophagy and Atherosclerosismentioning

confidence: 99%

Dual Role of Mitophagy in Cardiovascular Diseases

Meng

Hou

et al. 2021

Journal of Cardiovascular Pharmacology

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Mitophagy is involved in the development of various cardiovascular diseases, such as atherosclerosis, heart failure, myocardial ischemia/reperfusion injury, and hypertension. Mitophagy is essential for maintaining intracellular homeostasis and physiological function in most cardiovascular origin cells, such as cardiomyocytes, endothelial cells, and vascular smooth muscle cells. Mitophagy is crucial to ensuring energy supply by selectively removing dysfunctional mitochondria, maintaining a balance in the number of mitochondria in cells, ensuring the integrity of mitochondrial structure and function, maintaining homeostasis, and promoting cell survival. Substantial research has indicated a "dual" effect of mitophagy on cardiac function, with inadequate and increased mitochondrial degradation both likely to influence the progression of cardiovascular disease. This review summarizes the main regulatory pathways of mitophagy and emphasizes that an appropriate amount of mitophagy can prevent endothelial cell injury, vascular smooth muscle cell proliferation, macrophage polarization, and cardiomyocyte apoptosis, avoiding further progression of cardiovascular diseases.

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Section: Mitophagy and Atherosclerosismentioning

confidence: 99%

Dual Role of Mitophagy in Cardiovascular Diseases

Meng

Hou

et al. 2021

Journal of Cardiovascular Pharmacology

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“…Mitochondrial DNA mutations were found to be associated with atherosclerosis. 119 A direct relationship between the presence of some mtDNA mutations and defective mitophagy was also established in chronic inflammation-associated atherosclerotic disease. 147 Therefore, it is possible to suggest that mitochondrial mutations can be the cause of defective mitophagy (Fig.…”

Section: Defective Mitophagy and Mtdna Mutationsmentioning

confidence: 96%

“…In fact, defective mitophagy enhances and prolongs the inflammatory response and, thus, may be responsible for the chronification of inflammation. 6,82, 119 Improper mitophagy can lead to the accumulation of dysfunctional mitochondria, which release mtDNA and mitochondrial reactive oxygen species (mtROS) into the cytosol. 120 These molecules can activate intracellular signaling pathways that promote the production of inflammatory cytokines, such as IL1β, IL6, and tumor necrosis factor-alpha, and contribute to the development of chronic inflammation.…”

Section: Defective Mitophagy and Inflammatory Responsementioning

confidence: 99%

Role of Mitochondria in the Chronification of Inflammation: Focus on Dysfunctional Mitophagy and Mitochondrial DNA Mutations

Orekhov,

Summerhill,

Khotina

et al. 2023

Gene Expr

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Inflammation is a natural reaction of the innate immune system that evolved primarily to protect the human body from invading pathogens and to heal injuries. There are two different types of inflammation, acute and chronic inflammation, differing in duration, underlying causes, and characteristics. The acute-to-chronic transition can be determined by several pathomechanisms, including dysregulation of immune response and failure to eliminate the underlying cause. Moreover, epigenetic changes that refer to modifications in gene expression that are heritable but do not involve changes to the underlying DNA sequence can also contribute to prolonged inflammation. Emerging evidence suggests that dysfunctional mitochondria can promote the development of chronic inflammation. In this respect, the mechanisms triggering defective mitophagy, a selective form of autophagy that exterminates dysfunctional mitochondria to maintain cellular homeostasis, attracted special attention. The hypothesis on the pivotal role of mutations in mitochondrial DNA causing defective mitophagy stimulated the area of the research that applies editing of the mitochondrial genome. The mitoCAS9 vector and two single guide RNAs to the G15059A mutation were used to eliminate the mutation from the macrophage-like cells. The normal activity of the initially defective mitophagy was restored in intact macrophage-like cells, confirming the causal role of the G15059A mutation in the disruption of the mitophagy process. The unraveling of the underlying mechanisms of chronic inflammation will help to develop targeted therapeutic approaches aimed at restoring mitochondrial health and alleviating chronic inflammation that can be used for the treatment of a wide range of chronic inflammatory diseases.

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“…After monocytes have differentiated into macrophages, they excessively absorb modified LDL and may transform into foam cells. This leads to the formation of atherosclerotic plaques [ 12 ]. Further, macrophages continue to populate the atherosclerotic plaque by attracting new cells from the vascular bed and proliferation of resident cells located in the surrounding tissues.…”

Section: Introductionmentioning

confidence: 99%

The Role of Cytokines in Cholesterol Accumulation in Cells and Atherosclerosis Progression

Markin

Markina

Bogatyreva

et al. 2023

IJMS

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Atherosclerosis is the most common cardiovascular disease and is the number one cause of death worldwide. Today, atherosclerosis is a multifactorial chronic inflammatory disease with an autoimmune component, accompanied by the accumulation of cholesterol in the vessel wall and the formation of atherosclerotic plaques, endothelial dysfunction, and chronic inflammation. In the process of accumulation of atherogenic lipids, cells of the immune system, such as monocytes, macrophages, dendritic cells, etc., play an important role, producing and/or activating the production of various cytokines—interferons, interleukins, chemokines. In this review, we have tried to summarize the most important cytokines involved in the processes of atherogenesis.

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Genetics of Arterial-Wall-Specific Mechanisms in Atherosclerosis: Focus on Mitochondrial Mutations

Cited by 9 publications

References 82 publications

Dual Role of Mitophagy in Cardiovascular Diseases

Dual Role of Mitophagy in Cardiovascular Diseases

Role of Mitochondria in the Chronification of Inflammation: Focus on Dysfunctional Mitophagy and Mitochondrial DNA Mutations

The Role of Cytokines in Cholesterol Accumulation in Cells and Atherosclerosis Progression

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