Differential Telomere Shortening in Blood versus Arteries in an Animal Model of Type 2 Diabetes

Tajbakhsh, Samira; Aliakbari, Kamelya; Hussey, Damian J.; Lower, Karen M.; Donato, Anthony J.; Sokoya, Elke M.

doi:10.1155/2015/153829

Cited by 6 publications

(3 citation statements)

References 65 publications

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“…This is also important as a recent cross-sectional study demonstrated that telomere length is independently associated with subclinical atherosclerosis in subjects with T2D ( 152 ). However, accelerated telomere attrition was recently reported in circulating leukocytes, but not arteries, in T2D compared to control rats ( 156 ). This indicates the importance of immune senescence in diabetic vascular dysfunction/aging pathogenesis and that leukocytes may be primary targets of accelerated aging.…”

Section: Accelerated Vascular Aging In Diabetesmentioning

confidence: 95%

Epigenetics and Immunometabolism in Diabetes and Aging

Guzik

Cosentino

2018

Antioxidants & Redox Signaling

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Significance: A strong relationship between hyperglycemia, impaired insulin pathway, and cardiovascular disease in type 2 diabetes (T2D) is linked to oxidative stress and inflammation. Immunometabolic pathways link these pathogenic processes and pose important potential therapeutic targets.Recent Advances: The link between immunity and metabolism is bidirectional and includes the role of inflammation in the pathogenesis of metabolic disorders such as T2D, obesity, metabolic syndrome, and hypertension and the role of metabolic factors in regulation of immune cell functions. Low-grade inflammation, oxidative stress, balance between superoxide and nitric oxide, and the infiltration of macrophages, T cells, and B cells in insulin-sensitive tissues lead to metabolic impairment and accelerated aging.Critical Issues: Inflammatory infiltrate and altered immune cell phenotype precede development of metabolic disorders. Inflammatory changes are tightly linked to alterations in metabolic status and energy expenditure and are controlled by epigenetic mechanisms.Future Directions: A better comprehension of these mechanistic insights is of utmost importance to identify novel molecular targets. In this study, we describe a complex scenario of epigenetic changes and immunometabolism linking to diabetes and aging-associated vascular disease. Antioxid. Redox Signal. 29, 257–274.

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Section: Accelerated Vascular Aging In Diabetesmentioning

confidence: 95%

Epigenetics and Immunometabolism in Diabetes and Aging

Guzik

Cosentino

2018

Antioxidants & Redox Signaling

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“…eNOS, endothelial nitric oxide synthase. a reduction in the cellular redox status and an increase in oxidant stress may work together to reduce vascular SIRT1 expression (24)(25)(26). Furthermore, eNOS expression levels have also been shown to be low within cerebral arteries, which implies a connection between SIRT1 and eNOS (27).…”

Section: Discussionmentioning

confidence: 99%

Overexpressed eNOS upregulates SIRT1 expression and protects mouse pancreatic β cells from apoptosis

Chen

Jiang

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Loss of sirtuin 1 (SIRT1) activity may be associated with metabolic diseases, including diabetes. The aim of the present study was to investigate the potential effects of overexpressed endothelial nitric oxide synthase (eNOS) on cell proliferation and apoptosis with SIRT1 activation in the Min6 mouse pancreatic β cell line. A pcDNA3.0-eNOS plasmid was constructed and transfected into Min6 cells for 24 h prior to harvesting. eNOS expression was validated and SIRT1 expression was detected following plasmid transfection using reverse transcription-quantitative polymerase chain reaction and western blot analysis, which demonstrated that the expression levels of eNOS and SIRT1 were significantly upregulated. Furthermore, the cell proliferation and cell apoptosis of the Min6 cells were evaluated, using a cell counting kit-8 assay and flow cytometry, respectively. The results suggested that overexpressed eNOS promoted cell proliferation and inhibited cell apoptosis in Min6 cells. The interaction between eNOS and SIRT1 was explored through co-immunoprecipitation, and it found that there was a strong interaction between eNOS and SIRT1. In conclusion, overexpressed eNOS may induce SIRT1 activation, which is implied to play a protective role in Min6 cells, and eNOS may be a new therapeutic target for diseases such as type 2 diabetes.

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“…Immunoblotting was performed in lysates from pooled cerebral arteries (basilar artery, anterior, and posterior communicating arteries). Protein expression of eNOS‐P and total eNOS was measured as previously described (Tajbakhsh et al, 2015 ). The primary antibodies were mouse anti‐eNOS monocloncal primary antibody (BD Transduction Labs, 610296 at 1:1000 dilution) or rabbit anti‐eNOS‐P polyclonal primary antibody (Cell Signaling Technology, 9571 at 1:400 dilution).…”

Section: Methodsmentioning

confidence: 99%

Microbial disruption in the gut promotes cerebral endothelial dysfunction

Rustia

Paterson

Best

et al. 2021

Physiological Reports

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Cerebrovascular disease is a group of conditions characterized by disorders of the cerebral vessels. Endothelial dysfunction renders the vasculature at risk of impaired blood flow and increases the potential of developing cerebrovascular disease. The gut microbiota has been recently identified as a possible risk factor of cerebrovascular disease. However, a direct link between gut microbiota and cerebral vascular function has not been established. Therefore, the aim of this study was to determine the effect of gut bacterial disruption on cerebral endothelial function. Male inbred Sprague‐Dawley rats were randomly assigned to receive either drinking water with (n = 4) or without (n = 4) a cocktail of nonabsorbable broad‐spectrum antibiotics (streptomycin, neomycin, bacitracin, and polymyxin B). Three weeks of antibiotic treatment resulted in a significant reduction in bacterial load and shifts within the bacterial sub‐populations as assessed using flow cytometry. Using pressure myography, we found that spontaneous tone significantly increased and L‐NAME‐induced vasoconstriction was significantly blunted in middle cerebral arteries (MCAs) harvested from antibiotic‐treated rats. ATP‐mediated dilations were significantly blunted in MCAs from antibiotic‐treated rats compared to their control counterparts. Immunoblotting revealed that the eNOS‐P/total eNOS ratio was significantly reduced in cerebral artery lysates from antibiotic‐treated rats compared to controls. Our findings suggest that disruption of the gut microbiota leads to cerebral endothelial dysfunction through reduction of eNOS activity. This study highlights the potential of the microbiota as a target to reverse endothelial dysfunction and a preventative approach to reducing risk of stroke and aneurysms.

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Differential Telomere Shortening in Blood versus Arteries in an Animal Model of Type 2 Diabetes

Cited by 6 publications

References 65 publications

Epigenetics and Immunometabolism in Diabetes and Aging

Epigenetics and Immunometabolism in Diabetes and Aging

Overexpressed eNOS upregulates SIRT1 expression and protects mouse pancreatic β cells from apoptosis

Microbial disruption in the gut promotes cerebral endothelial dysfunction

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