Mitochondrial Dysfunction in Atherosclerosis

Peng, Wenxi; Cai, Guoding; Xia, Yiping; Chen, Jinna; Wu, Peng; Wang, Zuo; Li, Guohua; Wei, Dangheng

doi:10.1089/dna.2018.4552

Cited by 101 publications

(76 citation statements)

References 79 publications

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“…eNOS activity requires the participation of many cofactors, including tetrahydrobiopterin (BH 4 ); therefore, BH 4 availability is key for eNOS malfunctioning, as superoxide synthesis occurs in this situation instead [ 56 ]. In this scenario, higher superoxide production reacts with NO yielding peroxynitrite, which reduces NO bioavailability and induces protein nitration [ 57 , 58 ]. In addition, inducible nitric oxide synthase activation (iNOS) seems to be involved in eNOS uncoupling, since its activity occurs as a burst that promotes cofactor depletion in response to pro-inflammatory signals [ 24 , 59 ].…”

Section: Pro-atherosclerotic Oxidative Stress Mechanismsmentioning

confidence: 99%

The Interplay between Oxidative Stress and miRNAs in Obesity-Associated Hepatic and Vascular Complications

et al. 2020

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Nowadays, the obesity pandemic is one of the most relevant health issues worldwide. This condition is tightly related to comorbidities such as non-alcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVDs), namely atherosclerosis. Dysregulated lipid metabolism and inflammation link these three diseases, leading to a subsequent increase of oxidative stress (OS) causing severe cellular damage. On the other hand, microRNAs (miRNAs) are short, single-stranded, non-coding RNAs that act as post-transcriptional negative regulators of gene expression, thus being involved in the molecular mechanisms that promote the development of many pathologies including obesity and its comorbidities. The involvement of miRNAs in promoting or opposing OS in disease progression is becoming more evident. Some miRNAs, such as miR-200a and miR.421, seem to play important roles in OS control in NAFLD. On the other hand, miR-92a and miR-133, among others, are important in the development of atherosclerosis. Moreover, since both diseases are linked to obesity, they share common altered miRNAs, being miR-34a and miR-21 related to OS. This review summarizes the latest advances in the knowledge about the mechanisms of oxidative stress (OS) generation in obesity-associated NAFLD and atherosclerosis, as well as the role played by miRNAs in the regulation of such mechanisms.

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Section: Pro-atherosclerotic Oxidative Stress Mechanismsmentioning

confidence: 99%

The Interplay between Oxidative Stress and miRNAs in Obesity-Associated Hepatic and Vascular Complications

et al. 2020

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“…Mitochondrial stress and injury are known to trigger pro‐inflammatory NFκB activation via endosomal TLR9 binding mitochondrial CpG‐rich DNA 3–9 . The ability of CpG‐rich mitochondrial DNA to trigger TLR9 activation has led to the appropriate use of CpG‐ODN for the study of multiple disease states where mitochondrial stress and injury are believed to play a pathogenic role 51–56 . These include atherosclerosis, 10–14 ischaemia‐reperfusion, 11,15–19,94 infection/sepsis, 20–37 and various autoimmune diseases 38–50 .…”

Section: Discussionmentioning

confidence: 99%

“…CpG‐ODN has been used to study atherosclerosis, 10–14 ischaemia‐reperfusion, 11,15–19 infection/sepsis, 20–37 and various autoimmune diseases 38–50 . Importantly, mitochondrial stress and injury has also been implicated in the pathogenesis of atherosclerosis, 51 ischaemia‐reperfusion, 52,53 infection, 54,55 and various autoimmune diseases 56 . However, mitochondrial stress and injury leads to other pathological changes that impact innate immune signalling beyond CpG‐rich DNA release 57–60 .…”

Section: Introductionmentioning

confidence: 99%

CpG‐ODN‐mediated TLR9 innate immune signalling and calcium dyshomeostasis converge on the NFκB inhibitory protein IκBβ to drive IL1α and IL1β expression

et al. 2020

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Sterile inflammation contributes to many pathological states associated with mitochondrial injury. Mitochondrial injury disrupts calcium homeostasis and results in the release of CpG-rich mitochondrial DNA. The role of CpG-stimulated TLR9 innate immune signalling and sterile inflammation is well studied; however, how calcium dyshomeostasis affects this signalling is unknown. Therefore, we interrogated the relationship besween intracellular calcium and CpG-induced TLR9 signalling in murine macrophages. We found that CpG-ODN-induced NFjB-dependent IL1a and IL1b expression was significantly attenuated by both calcium chelation and calcineurin inhibition, a finding mediated by inhibition of degradation of the NFjB inhibitory protein IjBb. In contrast, calcium ionophore exposure increased CpG-induced IjBb degradation and IL1a and IL1b expression. These results demonstrate that through its effect on IjBb degradation, increased intracellular Ca 2+ drives a pro-inflammatory TLR9-mediated innate immune response. These results have implications for the study of innate immune signalling downstream of mitochondrial stress and injury.

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“…Thus, according to the modern understanding of the pathogenesis of cardiovascular diseases, mitochondrial dysfunction plays a significant role in the development of atherosclerosis and related complications (Marzetti et al 2013;Chistiakov et al 2018). Such changes in endotheliocytes and myocytes of the vessel wall lead to structural and functional disorders, manifested in the progression of atherosclerosis, hypertension and susceptibility to thrombosis (Peng et al 2019). Dysfunction of mitochondria in other cells, including neurons and cardiomyocytes, leads to a decrease in their resistance to ischaemia, which is manifested in an increase in lethal outcomes against the background of brain stroke, coronary artery occlusion, infarction of kidneys and other organs.…”

Section: Endothelial and Mitochondrial Dysfunction In The Developmentmentioning

confidence: 99%

Non-hematopoietic erythropoietin-derived peptides for atheroprotection and treatment of cardiovascular diseases

Belyaeva¹,

Stepenko²,

Lyubimov³

et al. 2020

RRP

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Relevance: Cardiovascular diseases continue to be the leading cause of premature adult death. Lipid profile and atherogenesis: Dislipidaemia leads to subsequent lipid accumulation and migration of immunocompetent cells into the vessel intima. Macrophages accumulate cholesterol forming foam cells – the morphological substrate of atherosclerosis in its initial stage. Inflammation and atherogenesis: Pro-inflammatory factors provoke oxidative stress, vascular wall damage and foam cells formation. Endothelial and mitochondrial dysfunction in the development of atherosclerosis: Endothelial mitochondria are some of the organelles most sensitive to oxidative stress. Damaged mitochondria produce excess superoxide and H2O2, which are the main factors of intracellular damage, further increasing endothelial dysfunction. Short non-hematopoietic erythropoietin-based peptides as innovative atheroprotectors: Research in recent decades has shown that erythropoietin has a high cytoprotective activity, which is mainly associated with exposure to the mitochondrial link and has been confirmed in various experimental models. There is also a short-chain derivative, the 11-amino acid pyroglutamate helix B surface peptide (PHBSP), which selectively binds to the erythropoietin heterodymic receptor and reproduces its cytoprotective properties. This indicates the promising use of short-chain derivatives of erythropoietin for the treatment and prevention of atherosclerotic vascular injury. In the future, it is planned to study the PHBSP derivatives, the modification of which consists in adding RGD and PGP tripeptides with antiaggregant properties to the original 11-member peptide.

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Mitochondrial Dysfunction in Atherosclerosis

Cited by 101 publications

References 79 publications

The Interplay between Oxidative Stress and miRNAs in Obesity-Associated Hepatic and Vascular Complications

The Interplay between Oxidative Stress and miRNAs in Obesity-Associated Hepatic and Vascular Complications

CpG‐ODN‐mediated TLR9 innate immune signalling and calcium dyshomeostasis converge on the NFκB inhibitory protein IκBβ to drive IL1α and IL1β expression

Non-hematopoietic erythropoietin-derived peptides for atheroprotection and treatment of cardiovascular diseases

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