Replicative senescence promotes prothrombotic responses in endothelial cells: Role of NADPH oxidase- and cyclooxygenase-derived oxidative stress

Silva, Grazielle C.; Abbas, Malak; Khemais‐Benkhiat, Sonia; Burban, Mélanie; Ribeiro, Thais Porto; Toti, Florence; Idris‐Khodja, Noureddine; Côrtes, Steyner F.; Schini‐Kerth, Valérie B.

doi:10.1016/j.exger.2017.04.006

Cited by 30 publications

(24 citation statements)

References 45 publications

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“…It has been postulated that the pathologic process of thrombosis begins with endothelial injury, and subsequently depends largely on a function of platelets, coagulation factors, and antithrombotic and fibrinolytic systems. Age-related endothelial dysfunction involves upregulation of the NADPH oxidase (NOX)-and cyclooxygenases (COXs)-dependent oxidative stress pathways [13], and overexpression of the antioxidant enzyme glutathione peroxidase 1 (GPX-1) protects from age-dependent increased venous thrombosis [14]. Oxidative stress and enhanced ROS production down-regulate the protective nitric oxide (NO) pathway, since reducing oxidative stress by the antioxidant vitamin C restores NO availability [15].…”

Section: Oxidative Stress Contribution To Venous Thrombosis During Agingmentioning

confidence: 99%

Oxidative Stress and Thrombosis during Aging: The Roles of Oxidative Stress in RBCs in Venous Thrombosis

Wang

Zennadi

2020

IJMS

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Mid-life stage adults are at higher risk of developing venous thrombosis (VT)/thromboembolism (VT/E). Aging is characterized by an overproduction of reactive oxygen species (ROS), which could evoke a series of physiological changes involved in thrombosis. Here, we focus on the critical role of ROS within the red blood cell (RBC) in initiating venous thrombosis during aging. Growing evidence has shifted our interest in the role of unjustifiably unvalued RBCs in blood coagulation. RBCs can be a major source of oxidative stress during aging, since RBC redox homeostasis is generally compromised due to the discrepancy between prooxidants and antioxidants. As a result, ROS accumulate within the RBC due to the constant endogenous hemoglobin (Hb) autoxidation and NADPH oxidase activation, and the uptake of extracellular ROS released by other cells in the circulation. The elevated RBC ROS level affects the RBC membrane structure and function, causing loss of membrane integrity, and decreased deformability. These changes impair RBC function in hemostasis and thrombosis, favoring a hypercoagulable state through enhanced RBC aggregation, RBC binding to endothelial cells affecting nitric oxide availability, RBC-induced platelet activation consequently modulating their activity, RBC interaction with and activation of coagulation factors, increased RBC phosphatidylserine exposure and release of microvesicles, accelerated aging and hemolysis. Thus, RBC oxidative stress during aging typifies an ultimate mechanism in system failure, which can affect major processes involved in the development of venous thrombosis in a variety of ways. The reevaluated concept of the critical role of RBC ROS in the activation of thrombotic events during aging will help identify potential targets for novel strategies to prevent/reduce the risk for VT/E or VT/E recurrences in mid-life stage adults.

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Section: Oxidative Stress Contribution To Venous Thrombosis During Agingmentioning

confidence: 99%

Oxidative Stress and Thrombosis during Aging: The Roles of Oxidative Stress in RBCs in Venous Thrombosis

Wang

Zennadi

2020

IJMS

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“…Several cellular stresses including oxidative stress, angiotensin II, high glucose, and reduced availability of NO are associated with the induction of premature endothelial senescence, which causes the upregulation of the cyclin-dependent kinase inhibitors p53, p21, and p16, leading to cell cycle arrest [20]. Moreover, replicative endothelial senescence is associated with an upregulation of the angiotensin system (ACE, AT1R) and NADPH oxidase and increased oxidative stress [19,22]. The present study shows an upregulation of p53, p21, and p16 in the old aorta, suggesting the induction of vascular senescence, which is normalized by the EPA:DHA 6:1 treatment.…”

Section: Bothmentioning

confidence: 99%

“…Premature endothelial senescence is observed in response to several pro-oxidant stimuli such as H2O2, Ang II, and elevated glucose concentration [19,20]. These prosenescence inducers promote the downregulation of eNOS and the induction of a proinflammatory and pro-atherothrombotic phenotype in endothelial cells [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Intake of omega-3 formulation EPA:DHA 6:1 by old rats for 2 weeks improved endothelium-dependent relaxations and normalized the expression level of ACE/AT1R/NADPH oxidase and the formation of ROS in the mesenteric artery

Farooq

Gærtner

Amoura

et al. 2020

Biochemical Pharmacology

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HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

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“…Importantly, elimination of senescent cells expressing the cell cycle regulator protein p16INK4A extends lifespan and health span in mice, reducing the inflammatory status of many organs (Baker et al 2016). Activation of cellular senescence programs have also been suggested to contribute to vascular pathology (Regina et al 2016;Wang et al 2015;Yamazaki et al 2016;Uryga and Bennett 2016;Gardner et al 2015;Liu et al 2018;Silva et al 2017;Matthews et al 2006). Despite these advances, the role of senescence in cerebrovascular aging remains unexplored.…”

Section: Introductionmentioning

confidence: 99%

Nrf2 deficiency in aged mice exacerbates cellular senescence promoting cerebrovascular inflammation

et al. 2018

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Aging-induced pro-inflammatory phenotypic alterations of the cerebral vasculature critically contribute to the pathogenesis of vascular cognitive impairment. Cellular senescence is a fundamental aging process that promotes inflammation; however, its role in cerebrovascular aging remains unexplored. The present study was undertaken to test the hypothesis that advanced aging promotes cellular senescence in the cerebral vasculature. We found that in cerebral arteries of 24-month-old mice, expression of molecular markers of senescence (p16 INK4a , p21) is upregulated as compared to that in young controls. Induction of senescence programs in cerebral arteries is associated by an upregulation of a wide range of inflammatory cytokines and chemokines, which are known to contribute to the senescence-associated secretory phenotype (SASP) in vascular cells. Age-related cerebrovascular senescence and inflammation are associated with neuroinflammation, as shown by the molecular footprint of microglia activation in the hippocampus. Genetic depletion of the pro-survival/anti-aging transcriptional regulator Nrf2 exacerbated age-related induction of senescence markers and inflammatory SASP factors and resulted in a heightened inflammatory status of the hippocampus. In conclusion, our studies provide evidence that aging and Nrf2 dysfunction promote cellular senescence in cerebral vessels, which may potentially cause or exacerbate age-related pathology.

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Replicative senescence promotes prothrombotic responses in endothelial cells: Role of NADPH oxidase- and cyclooxygenase-derived oxidative stress

Cited by 30 publications

References 45 publications

Oxidative Stress and Thrombosis during Aging: The Roles of Oxidative Stress in RBCs in Venous Thrombosis

Oxidative Stress and Thrombosis during Aging: The Roles of Oxidative Stress in RBCs in Venous Thrombosis

Intake of omega-3 formulation EPA:DHA 6:1 by old rats for 2 weeks improved endothelium-dependent relaxations and normalized the expression level of ACE/AT1R/NADPH oxidase and the formation of ROS in the mesenteric artery

Nrf2 deficiency in aged mice exacerbates cellular senescence promoting cerebrovascular inflammation

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