Mitochondrial Dysfunction in Vascular Wall Cells and Its Role in Atherosclerosis

Salnikova, Diana I.; Orekhova, Varvara A.; Grechko, Andrey V.; Стародубова, А В; Bezsonov, Evgeny E.; Popkova, Tatyana; Orekhov, Alexander N.

doi:10.3390/ijms22168990

Cited by 46 publications

(32 citation statements)

References 113 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[25] The regulation of the release of Cytochrome C is also modulated by Bcl-2 family proteins, such as anti-apoptotic (e.g., Bcl-2 and Bcl-xL) and pro-apoptotic (e.g., Bad, Bak, and Bax) ones. [26] In the present study, AR-C17 significantly reduced ox-LDL caused HUVECs apoptosis and dysfunction by reducing mtROS production, Cytochrome C release, and the ratio of Bax/Bcl-2, while improving mitochondrial membrane integrity. The anti-apoptosis ability of AR-C17 on HUVECs was possibly ascribed to its strong anti-oxidative activity, which was in consistent with previous study indicating AR-C17 attenuated oxidative injury and mitochondria-dependent apoptosis in neurocytes.…”

Section: Discussionsupporting

confidence: 54%

“…Furthermore, remodeling of mitochondrial network occurs in response to cellular stress and various pathological conditions. [ 26 ] Maintaining mitochondrial homeostasis is vital for heart function, including cardiomyocyte metabolism and contractile function, whereas defect in mitochondrial dynamics is a key factor in the pathophysiology of CVDs. [ 28 ] Mitochondria dynamics involve constant fission and fusion processes which are regulated mainly by fusion proteins (MFN1, MFN2) and fission proteins (DRP1, FIS1).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

5‐Heptadecylresorcinol Protects against Atherosclerosis in Apolipoprotein E‐Deficient Mice by Modulating SIRT3 Signaling: The Possible Beneficial Effects of Whole Grain Consumption

Hao

Yang

et al. 2022

Molecular Nutrition Food Res

View full text Add to dashboard Cite

Scope Whole grain consumption has been proven to be inversely associated with the risk of cardiovascular diseases. As a biomarker for whole grain dietary intake, 5‐heptadecylresorcinol (AR‐C17) has attracted increased attention due to its potential health‐improving activity. However, the beneficial effect of AR‐C17 on atherosclerosis prevention and the underlying mechanism remain unclear. Methods and Results High‐fat diet fed apolipoprotein E‐deficient (ApoE−/−) mice are administrated with or without AR‐C17 (30 and 150 mg kg−1) for 16 weeks. Histological staining is performed for plaque analysis. Immunofluorescence, western blot, and seahorse cell analysis are carried out to investigate the action of mechanism of AR‐C17. The results indicate that AR‐C17 supplementation lowered serum total cholesterol, triglyceride, VLDL‐C, and LDL‐C levels. Moreover, the atherosclerotic plaques in the aortic root region of mice heart are significantly reduced by AR‐C17 intervention compared with ApoE−/− control group. In addition, AR‐C17 treatment alleviates endothelial cell damage and apoptosis by improving mitochondrial function via sirtuin3 signaling pathway both in ApoE−/− mice and oxidized‐LDL‐treated human umbilical vein endothelial cells. Conclusion AR‐C17 may be applied as a promising grain‐based dietary bioactive ingredient for atherosclerosis prevention. Meanwhile, as a mitochondrial protective agent, it can offer support for the suggested health claim of whole grain diet.

show abstract

Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

5‐Heptadecylresorcinol Protects against Atherosclerosis in Apolipoprotein E‐Deficient Mice by Modulating SIRT3 Signaling: The Possible Beneficial Effects of Whole Grain Consumption

Hao

Yang

et al. 2022

Molecular Nutrition Food Res

View full text Add to dashboard Cite

show abstract

“…Increasing evidences reveals that mitochondrial dysfunction also contributes to atherosclerosis. In the early stage of atherosclerosis, increased production of reactive oxygen species (ROS) in mitochondria, accumulation of mitochondrial DNA (mtDNA) damage, and progressive respiratory chain dysfunction, resulted in endothelial cells (ECs) dysfunction and vascular smooth muscle cells (VSMCs) phenotypic conversion 17 . After a long term, ECs apoptosis, VSMCs phenotypic conversion, and inflammatory cells infiltration further promoted the development of atherosclerosis and led to vulnerable plaque in the end.…”

Section: Introductionmentioning

confidence: 99%

Pitavastatin activates mitophagy to protect EPC proliferation through a calcium-dependent CAMK1-PINK1 pathway in atherosclerotic mice

et al. 2022

View full text Add to dashboard Cite

Statins play a major role in reducing circulating cholesterol levels and are widely used to prevent coronary artery disease. Although they are recently confirmed to up-regulate mitophagy, little is known about the molecular mechanisms and its effect on endothelial progenitor cell (EPC). Here, we explore the role and mechanism underlying statin (pitavastatin, PTV)-activated mitophagy in EPC proliferation. ApoE−/− mice are fed a high-fat diet for 8 weeks to induce atherosclerosis. In these mice, EPC proliferation decreases and is accompanied by mitochondrial dysfunction and mitophagy impairment via the PINK1-PARK2 pathway. PTV reverses mitophagy and reduction in proliferation. Pink1 knockout or silencing Atg7 blocks PTV-induced proliferation improvement, suggesting that mitophagy contributes to the EPC proliferation increase. PTV elicits mitochondrial calcium release into the cytoplasm and further phosphorylates CAMK1. Phosphorylated CAMK1 contributes to PINK1 phosphorylation as well as mitophagy and mitochondrial function recover in EPCs. Together, our findings describe a molecular mechanism of mitophagy activation, where mitochondrial calcium release promotes CAMK1 phosphorylation of threonine177 before phosphorylation of PINK1 at serine228, which recruits PARK2 and phosphorylates its serine65 to activate mitophagy. Our results further account for the pleiotropic effects of statins on the cardiovascular system and provide a promising and potential therapeutic target for atherosclerosis.

show abstract

“…Mitochondrial respiratory chain enzyme dysfunction leads to an increased ROS production. Experiments involving the deletion of antioxidant systems in ApoE−/− mice suggest a role for mitochondrial ROS in atherogenesis [ 92 , 93 , 94 ].…”

Section: Atherosclerosis Pathophysiological Processmentioning

confidence: 99%

“…Experiments involving the deletion of antioxidant systems in ApoE−/− mice suggest a role for mitochondrial ROS in atherogenesis [92][93][94].…”

Section: Oxidative Stress In Atherosclerosismentioning

confidence: 99%

Inflammation, Oxidative Stress, Senescence in Atherosclerosis: Thioredoxine-1 as an Emerging Therapeutic Target

Hadri

Smith

Duplus

et al. 2021

IJMS

View full text Add to dashboard Cite

Atherosclerosis is a leading cause of cardiovascular diseases (CVD) worldwide and intimately linked to aging. This pathology is characterized by chronic inflammation, oxidative stress, gradual accumulation of low-density lipoproteins (LDL) particles and fibrous elements in focal areas of large and medium arteries. These fibrofatty lesions in the artery wall become progressively unstable and thrombogenic leading to heart attack, stroke or other severe heart ischemic syndromes. Elevated blood levels of LDL are major triggering events for atherosclerosis. A cascade of molecular and cellular events results in the atherosclerotic plaque formation, evolution, and rupture. Moreover, the senescence of multiple cell types present in the vasculature were reported to contribute to atherosclerotic plaque progression and destabilization. Classical therapeutic interventions consist of lipid-lowering drugs, anti-inflammatory and life style dispositions. Moreover, targeting oxidative stress by developing innovative antioxidant agents or boosting antioxidant systems is also a well-established strategy. Accumulation of senescent cells (SC) is also another important feature of atherosclerosis and was detected in various models. Hence, targeting SCs appears as an emerging therapeutic option, since senolytic agents favorably disturb atherosclerotic plaques. In this review, we propose a survey of the impact of inflammation, oxidative stress, and senescence in atherosclerosis; and the emerging therapeutic options, including thioredoxin-based approaches such as anti-oxidant, anti-inflammatory, and anti-atherogenic strategy with promising potential of senomodulation.

show abstract

Mitochondrial Dysfunction in Vascular Wall Cells and Its Role in Atherosclerosis

Cited by 46 publications

References 113 publications

5‐Heptadecylresorcinol Protects against Atherosclerosis in Apolipoprotein E‐Deficient Mice by Modulating SIRT3 Signaling: The Possible Beneficial Effects of Whole Grain Consumption

5‐Heptadecylresorcinol Protects against Atherosclerosis in Apolipoprotein E‐Deficient Mice by Modulating SIRT3 Signaling: The Possible Beneficial Effects of Whole Grain Consumption

Pitavastatin activates mitophagy to protect EPC proliferation through a calcium-dependent CAMK1-PINK1 pathway in atherosclerotic mice

Inflammation, Oxidative Stress, Senescence in Atherosclerosis: Thioredoxine-1 as an Emerging Therapeutic Target

Contact Info

Product

Resources

About