Ageing enhances the shedding of splenocyte microvesicles with endothelial pro-senescent effect that is prevented by a short-term intake of omega-3 PUFA EPA:DHA 6:1

Qureshi, Abdul Wahid; Altamimy, Raed Adill Hannon; Habhab, Ali El; Itawi, Hanine El; Farooq, Muhammad; Zobairi, Fatiha; Hasan, Hira; Amoura, Lamia; Kassem, Mohamad; Auger, Cyril; Schini‐Kerth, Valérie B.; Toti, Florence

doi:10.1016/j.bcp.2019.113734

Cited by 16 publications

(8 citation statements)

References 48 publications

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“…Through modulation of the physical properties of membranes, EPA provides a specific environment to support the function of membrane proteins, such as receptors, transporters, ion channels, and signaling enzymes [ 24 ]. To date, substantial evidence has accumulated from prospective and case–control studies indicating that a higher intake of EPA is associated with a lower risk of adverse CVD outcomes in populations [ 25 , 26 ]. The conclusion that very-long-chain n-3 fatty acids have a role in reducing the risk of CVD, especially CHD, is fully supported by the American Heart Association [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Metabolomic Analysis of the Ameliorative Effect of Enhanced Proline Metabolism on Hypoxia-Induced Injury in Cardiomyocytes

Wang

Xue

Hua

et al. 2020

Oxidative Medicine and Cellular Longevity

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Background. Coronary heart disease is currently the leading cause of death in humans. Its poor prognosis and high mortality are associated with myocardial ischemia, which leads to metabolic disorder-related cardiomyocyte apoptosis and reactive oxygen species (ROS) production. Previous cardiovascular metabolomics studies in humans and mice have shown that proline metabolism is severely altered after cardiomyocyte hypoxia. Proline dehydrogenase (PRODH) is located on the inner mitochondrial membrane and is an enzyme that catalyzes the first step of proline catabolism, which plays an important role in improving the cellular redox state. In vitro oxygen-glucose deprivation can mimic in vivo myocardial ischemic injury. This study is aimed at investigating whether enhancing proline metabolism by overexpressing PRODH can ameliorate hypoxia-induced injury in cardiomyocytes and to reveal the related altered metabolites and mechanistic pathway via untargeted metabolomics analysis. Methods and Results. First, through public database analysis and RT-qPCR and western blot analyses in a cardiomyocyte hypoxia model, we found that the expression of the proline-degrading enzyme PRODH was downregulated after myocardial infarction and hypoxia exposure. Second, LDH assays, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), DHE staining, flow cytometric apoptosis analysis with DCFH and Annexin V-FITC/PI, and western blot analysis were used to assess the injury level in cardiomyocytes. Enhanced proline metabolism induced by PRODH overexpression reduced the levels of reactive oxidative stress and apoptosis, whereas PRODH knockdown had the opposite effects. Third, untargeted metabolomics analysis revealed that the protective effect was associated with significant changes in metabolism linked to sphingolipid signaling pathways, unsaturated fatty acid biosynthesis, phosphocreatine, glutathione disulfide, aminoacyl-tRNA biosynthesis, and ABC transporters. Conclusions. Our study demonstrated a protective effect of enhanced proline metabolism in cardiomyocytes under hypoxia, providing a novel strategy for exploring new treatments for coronary heart disease.

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Section: Discussionmentioning

confidence: 99%

Metabolomic Analysis of the Ameliorative Effect of Enhanced Proline Metabolism on Hypoxia-Induced Injury in Cardiomyocytes

Wang

Xue

Hua

et al. 2020

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…Through modulation of the physical properties of membranes, EPA provides a speci c environment to support the function of membrane proteins, such as receptors, transporters, ion channels and signaling enzymes [22]. To date, substantial evidence has accumulated from prospective and case-control studies indicating that a higher intake of EPA is associated with a lower risk of adverse CVD outcomes in populations [23], [24]. The conclusion that very-long-chain n-3 fatty acids have a role in reducing the risk of CVD, especially CHD, is fully supported by the American Heart Association [25].…”

Section: Discussionmentioning

confidence: 99%

Metabolomics analysis of the ameliorative effect of enhanced proline metabolism on hypoxia-induced injury in cardiomyocytes

Wang

Xue

Hua

et al. 2020

Preprint

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Background Coronary heart disease is currently the leading cause of death in humans. Its poor prognosis and high mortality are associated with myocardial ischemia, which leads to metabolic disorder-related cardiomyocyte apoptosis and reactive oxygen species (ROS) production. Previous cardiovascular metabolomics studies in humans and mice have shown that proline metabolism is severely altered after cardiomyocyte hypoxia. Proline dehydrogenase (PRODH) is an enzyme that catalyzes the first step of proline catabolism, which plays an important role in improving the cellular redox state. In vitro oxygen-glucose deprivation can mimic in vivo myocardial ischemic injury. This study aimed to investigate whether enhancing proline metabolism by overexpressing PRODH can ameliorate hypoxia-induced injury in cardiomyocytes and to reveal the related altered metabolites and mechanistic pathway via untargeted metabolomics analysis. Results First, through public database analysis and RT-qPCR and western blot analyses in a cardiomyocyte hypoxia model, we found that the expression of the proline-degrading enzyme PRODH was downregulated after myocardial infarction and hypoxia exposure. Second, LDH assays, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), DHE staining, flow cytometric apoptosis analysis with DCFH and Annexin V-FITC/PI, and western blot analysis were used to assess the injury level in cardiomyocytes. Enhanced proline metabolism induced by PRODH overexpression reduced the levels of reactive oxidative stress and apoptosis, whereas PRODH knockdown had the opposite effects. Third, untargeted metabolomics analysis revealed that the protective effect was associated with significant changes in metabolism linked to sphingolipid signaling pathways, unsaturated fatty acid biosynthesis, phosphocreatine, glutathione disulfide, aminoacyl-tRNA biosynthesis, and ABC transporters. Conclusions Our study demonstrated a protective effect of enhanced proline metabolism in cardiomyocytes under hypoxia, providing a novel strategy for exploring new treatments for coronary heart disease.

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“…There is increasing evidence for an anti‐senescence role of EPA and DHA on ECs. A study from rats demonstrated that ingestion of EPA and DHA attenuated the pro‐senescence, pro‐inflammatory and pro‐thrombotic effects of microvesicles from cultured rat spleen‐derived leukocytes on ECs (Qureshi et al ., 2020). Another in vitro study supported these results, showing that either EPA or DHA attenuated hydrogen peroxide (H 2 O 2 )‐induced DNA damage, ROS production and cellular senescence in ECs through enhancing the Nrf2‐mediated antioxidant response (Sakai et al ., 2017).…”

Section: Evidence and Mechanisms Of Dyslipidemia‐induced Ec Senescenc...mentioning

confidence: 99%

New insight into dyslipidemia‐induced cellular senescence in atherosclerosis

Xiang

Tian

et al. 2022

Biological Reviews

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Atherosclerosis, characterized by lipid-rich plaques in the arterial wall, is an age-related disorder and a leading cause of mortality worldwide. However, the specific mechanisms remain complex. Recently, emerging evidence has demonstrated that senescence of various types of cells, such as endothelial cells (ECs), vascular smooth muscle cells (VSMCs), macrophages, endothelial progenitor cells (EPCs), and adipose-derived mesenchymal stem cells (AMSCs) contributes to atherosclerosis. Cellular senescence and atherosclerosis share various causative stimuli, in which dyslipidemia has attracted much attention. Dyslipidemia, mainly referred to elevated plasma levels of atherogenic lipids or lipoproteins, or functional impairment of anti-atherogenic lipids or lipoproteins, plays a pivotal role both in cellular senescence and atherosclerosis. In this review, we summarize the current evidence for dyslipidemia-induced cellular senescence during atherosclerosis, with a focus on low-density lipoprotein (LDL) and its modifications, hydrolysate of triglyceride-rich lipoproteins (TRLs), and high-density lipoprotein (HDL), respectively. Furthermore, we describe the underlying mechanisms linking dyslipidemia-induced cellular senescence and atherosclerosis. Finally, we discuss the senescence-related therapeutic strategies for atherosclerosis, with special attention given to the anti-atherosclerotic effects of promising geroprotectors as well as anti-senescence effects of current lipid-lowering drugs.

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Ageing enhances the shedding of splenocyte microvesicles with endothelial pro-senescent effect that is prevented by a short-term intake of omega-3 PUFA EPA:DHA 6:1

Cited by 16 publications

References 48 publications

Metabolomic Analysis of the Ameliorative Effect of Enhanced Proline Metabolism on Hypoxia-Induced Injury in Cardiomyocytes

Metabolomic Analysis of the Ameliorative Effect of Enhanced Proline Metabolism on Hypoxia-Induced Injury in Cardiomyocytes

Metabolomics analysis of the ameliorative effect of enhanced proline metabolism on hypoxia-induced injury in cardiomyocytes

New insight into dyslipidemia‐induced cellular senescence in atherosclerosis

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