Atherosclerosis Can Be Mitochondrial: A Review

Finsterer, Josef

doi:10.7759/cureus.6987

Cited by 7 publications

(11 citation statements)

References 31 publications

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“…The appearance of atherosclerosis in mitochondrial diseases may result from a primary pathological mechanism or as a consequence of a secondary mechanism associated with diabetes, arterial hypertension, or hyperlipidemia [ 152 ]. Most frequently, patients harboring mutations in mtDNA may develop primary mitochondrial atherosclerosis.…”

Section: The Role Of Mitochondria In Atherosclerosismentioning

confidence: 99%

From Mitochondria to Atherosclerosis: The Inflammation Path

et al. 2021

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Inflammation is a key process in metazoan organisms due to its relevance for innate defense against infections and tissue damage. However, inflammation is also implicated in pathological processes such as atherosclerosis. Atherosclerosis is a chronic inflammatory disease of the arterial wall where unstable atherosclerotic plaque rupture causing platelet aggregation and thrombosis may compromise the arterial lumen, leading to acute or chronic ischemic syndromes. In this review, we will focus on the role of mitochondria in atherosclerosis while keeping inflammation as a link. Mitochondria are the main source of cellular energy. Under stress, mitochondria are also capable of controlling inflammation through the production of reactive oxygen species (ROS) and the release of mitochondrial components, such as mitochondrial DNA (mtDNA), into the cytoplasm or into the extracellular matrix, where they act as danger signals when recognized by innate immune receptors. Primary or secondary mitochondrial dysfunctions are associated with the initiation and progression of atherosclerosis by elevating the production of ROS, altering mitochondrial dynamics and energy supply, as well as promoting inflammation. Knowing and understanding the pathways behind mitochondrial-based inflammation in atheroma progression is essential to discovering alternative or complementary treatments.

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Section: The Role Of Mitochondria In Atherosclerosismentioning

confidence: 99%

From Mitochondria to Atherosclerosis: The Inflammation Path

et al. 2021

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“…In atherosclerosis, the chronic inflammation, cell damage, and arterial vascular endothelial dysfunction initiated by a physical or chemical injury is exaggerated by vascular cell adhesion molecules-induced adherence of neutrophils, lymphocytes, and monocytes to the endothelial cells [172]. The resulting elevated permeability of the vascular endothelium to endothelial cells and smooth muscle cells is caused by endothelial glycocalyx disruption and inhibition of voltage-sensitive K + , and Ca 2+ -activated K + channels.…”

Section: Atherosclerosis and Myocardial Infarctionmentioning

confidence: 99%

“…In addition to contributing to the vascular inflammation and endothelial dysfunction, PARP1 can facilitate atherosclerotic plaque disruption by activating matrix metalloproteinases (MMPs) [174]. Moderate PARP activation leads to AIF or caspase-mediated apoptosis while overactivation causes atherosclerotic plaque disruption and necrotic cell death [172]. PARP inhibitors were demonstrated to ameliorate all these effects in various experimental systems [172][173][174].…”

Section: Atherosclerosis and Myocardial Infarctionmentioning

confidence: 99%

“…Moderate PARP activation leads to AIF or caspase-mediated apoptosis while overactivation causes atherosclerotic plaque disruption and necrotic cell death [172]. PARP inhibitors were demonstrated to ameliorate all these effects in various experimental systems [172][173][174]. Acute myocardial infarction is followed by reperfusion, due to either coronary thrombolytic therapy or surgical intervention [175].…”

Section: Atherosclerosis and Myocardial Infarctionmentioning

confidence: 99%

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Mitochondrial Protection by PARP Inhibition

Gallyas

Sümegi

2020

IJMS

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Inhibitors of the nuclear DNA damage sensor and signalling enzyme poly(ADP-ribose) polymerase (PARP) have recently been introduced in the therapy of cancers deficient in double-strand DNA break repair systems, and ongoing clinical trials aim to extend their use from other forms of cancer non-responsive to conventional treatments. Additionally, PARP inhibitors were suggested to be repurposed for oxidative stress-associated non-oncological diseases resulting in a devastating outcome, or requiring acute treatment. Their well-documented mitochondria- and cytoprotective effects form the basis of PARP inhibitors’ therapeutic use for non-oncological diseases, yet can limit their efficacy in the treatment of cancers. A better understanding of the processes involved in their protective effects may improve the PARP inhibitors’ therapeutic potential in the non-oncological indications. To this end, we endeavoured to summarise the basic features regarding mitochondrial structure and function, review the major PARP activation-induced cellular processes leading to mitochondrial damage, and discuss the role of PARP inhibition-mediated mitochondrial protection in several oxidative stress-associated diseases.

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“…At the same time, the effect of mutations of the mitochondrial genome is more significant for the formation of atherosclerotic lesions since mitochondrial dysfunction leads to activation of the key factors of atherogenesis, such as oxidative stress and inflammation [8]. Nowadays, the role of mitochondrial genome mutations in the predisposition to atherosclerosis development and cardiovascular disease is being investigated [9].…”

Section: Introductionmentioning

confidence: 99%

Impact of Mitochondrial DNA Mutations on Carotid Intima-Media Thickness in the Novosibirsk Region

Kirichenko

Рыжкова

Sinyov

et al. 2020

Life

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The search for markers of predisposition to atherosclerosis development is very important for early identification of individuals with a high risk of cardiovascular disease. The aim of the present study was to investigate the association of mitochondrial DNA mutations with carotid intima-media thickness and to determine the impact of mitochondrial heteroplasmy measurements in the prognosis of atherosclerosis development. This cross-sectional, population-based study was conducted in 468 subjects from the Novosibirsk region. It was shown that the mean (carotid intima-media thickness) cIMT correlated with the following mtDNA mutations: m.15059G>A (r = 0.159, p = 0.001), m.12315G>A (r = 0.119; p = 0.011), m.5178C>A (r = 0.114, p = 0.014), and m.3256C>T (r = 0.130, p = 0.011); a negative correlation with mtDNA mutations m.14846G>A (r = −0.111, p = 0.042) and m.13513G>A (r = −0.133, p = 0.004) was observed. In the linear regression analysis, the addition of the set of mtDNA mutations to the conventional cardiovascular risk factors increased the ability to predict the cIMT variability from 17 to 27%. Multi-step linear regression analysis revealed the most important predictors of mean cIMT variability: age, systolic blood pressure, blood levels of total cholesterol, LDL and triglycerides, as well as the mtDNA mutations m.13513G>A, m.15059G>A, m.12315G>A, and m.3256C>T. Thus, a high predictive value of mtDNA mutations for cIMT variability was demonstrated. The association of mutation m.13513G>A and m.14846G>A with a low value of cIMT, demonstrated in several studies, represents a potential for the development of anti-atherosclerotic gene therapy.

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Atherosclerosis Can Be Mitochondrial: A Review

Cited by 7 publications

References 31 publications

From Mitochondria to Atherosclerosis: The Inflammation Path

From Mitochondria to Atherosclerosis: The Inflammation Path

Mitochondrial Protection by PARP Inhibition

Impact of Mitochondrial DNA Mutations on Carotid Intima-Media Thickness in the Novosibirsk Region

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