Association between oxidative DNA damage and telomere shortening in circulating endothelial progenitor cells obtained from metabolic syndrome patients with coronary artery disease

Satoh, Mamoru; Ishikawa, Yuh; Takahashi, Yūji; Itoh, Tomonori; Minami, Yoshitaka; Nakamura, Motoyuki

doi:10.1016/j.atherosclerosis.2007.09.040

Cited by 134 publications

(110 citation statements)

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“…Reduced telomere length and telomerase activity may precede and predispose to cellular dysfunction with age (18). Moreover, endothelial progenitor cells from coronary artery disease patients with the metabolic syndrome have been shown to demonstrate significantly eroded telomere length and telomerase activity compared with those without the metabolic syndrome (33). In the current study, we observed a progressive decline in telomere length with age in CD31 ϩ T cells.…”

Section: Discussionsupporting

confidence: 61%

Human aging and CD31⁺T-cell number, migration, apoptotic susceptibility, and telomere length

Kushner

Weil

MacEneaney

et al. 2010

Journal of Applied Physiology

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Kushner EJ, Weil BR, MacEneaney OJ, Morgan RG, Mestek ML, Van Guilder GP, Diehl KJ, Stauffer BL, DeSouza CA. Human aging and CD31 ϩ T-cell number, migration, apoptotic susceptibility, and telomere length. J Appl Physiol 109: 1756 -1761. First published September 23, 2010 doi:10.1152/japplphysiol.00601.2010.-CD31 ϩ T cells, or so-called "angiogenic T cells," have been shown to demonstrate vasculoprotective and neovasculogenic qualities. The influence of age on CD31 ϩ T-cell number and function is unclear. We tested the hypothesis that circulating CD31 ϩ T-cell number and migratory capacity are reduced, apoptotic susceptibility is heightened, and telomere length is shortened with advancing age in adult humans. Thirtysix healthy, sedentary men were studied: 12 young (25 Ϯ 1 yr), 12 middle aged (46 Ϯ 1 yr), and 12 older (64 Ϯ 2 yr). CD31 ϩ T cells were isolated from peripheral blood samples by magnetic-activated cell sorting. The number of circulating CD31 ϩ T cells (fluorescenceactivated cell sorting analysis) was lower (P Ͻ 0.01) in older (24% of CD3 ϩ cells) compared with middle-aged (38% of CD3 ϩ cells) and young (40% of CD3 ϩ cells) men. Migration (Boyden chamber) to both VEGF and stromal cell-derived factor-1␣ was markedly blunted (P Ͻ 0.05) in cells harvested from middle-aged [306.1 Ϯ 45 and 305.6 Ϯ 46 arbitrary units (AU), respectively] and older (231 Ϯ 65 and 235 Ϯ 62 AU, respectively) compared with young (525 Ϯ 60 and 570 Ϯ 62 AU, respectively) men. CD31 ϩ T cells from middle-aged and older men demonstrated greater apoptotic susceptibility, as staurosporine-stimulated intracellular caspase-3 activation was ϳ40% higher (P Ͻ 0.05) than young. There was a progressive age-related decline in CD31 ϩ T-cell telomere length (young: 10,706 Ϯ 220 bp; middle-aged: 10,179 Ϯ 251 bp; and older: 9,324 Ϯ 192 bp). Numerical and functional impairments in this unique T-cell subpopulation may contribute to diminished angiogenic potential and greater cardiovascular risk with advancing age. age; apoptosis; vascular CD31 OR PLATELET/ENDOTHELIAL cell adhesion molecule (PECAM) is a glycoprotein present on the surface of immune cells including platelets, monocytes, and granulocytes (4, 38). The CD31 receptor globulin is composed of six extracellular immunoglobulin repeats followed by a transmembrane domain and two cytosolic immunoreceptor tyrosine inhibitory motifs that carry a diverse array of signaling consequences known to be involved in cell phenotype determination, gene expression, and cell cycle (29,30,36). The unique structural homology of CD31's extracellular region is responsible for facilitating numerous heterophilic and homophilic binding interactions between differing vascular tissues (10, 16). For example, CD31 is highly expressed in the border junctions of endothelial cells where it plays a role in endothelial cell motility and regulating leukocyte transendothelial migration (31). In CD31 knockout mice, endothelial cell motility and filopodia formation as well as neovascularization are markedly impaired (5).Recently,...

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Section: Discussionsupporting

confidence: 61%

Human aging and CD31⁺T-cell number, migration, apoptotic susceptibility, and telomere length

Kushner

Weil

MacEneaney

et al. 2010

Journal of Applied Physiology

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“…It has been reported that elderly healthy subjects had lower circulating EPCs with impaired function and increased senescence when compared to young people 25. Circulating EPCs obtained from CAD patients, compared with from age‐matched healthy subjects, showed shorter telomere length and lower telomerase activity 26. These emerging evidence supported that the decreased number and increased senescence of circulating EPCs in older CAD patients contribute to vascular endothelial dysfunction and ageing.…”

Section: Discussionmentioning

confidence: 63%

MicroRNA‐216a induces endothelial senescence and inflammation via Smad3/IκBα pathway

Yang

Chen

et al. 2018

J Cellular Molecular Medi

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Vascular endothelial senescence contributes to atherosclerosis and coronary artery disease (CAD), but the mechanisms are yet to be clarified. We identified that microRNA‐216a (miR‐216a) significantly increased in senescent endothelial cells. The replicative senescence model of human umbilical vein endothelial cells (HUVECs) was established to explore the role of miR‐216a in endothelial ageing and dysfunction. Luciferase assay indicated that Smad3 was a direct target of miR‐216a. Stable expression of miR‐216a induced a premature senescence‐like phenotype in HUVECs with an impairment in proliferation and migration and led to an increased adhesion to monocytes by inhibiting Smad3 expression and thereafter modulating the degradation of NF‐κB inhibitor alpha (IκBα) and activation of adhesion molecules. Conversely, inhibition of endogenous miR‐216a in senescent HUVECs rescued Smad3 and IκBα expression and inhibited monocytes attachment. Plasma miR‐216a was significantly higher in old CAD patients (>50 years) and associated with increased 31% risk for CAD (odds ratio 1.31, 95% confidence interval 1.03‐1.66; P = .03) compared with the matched healthy controls (>50 years). Taken together, our data suggested that miR‐216a promotes endothelial senescence and inflammation as an endogenous inhibitor of Smad3/IκBα pathway, which might serve as a novel target for ageing‐related atherosclerotic diseases.

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“…They suggest that telomere attrition in response to OxS may induce enhanced endothelial damage and contribute to increase the risk of subsequent cardiovascular events (Satoh et al 2008). Protein carbonyl plasma levels (a) and isoprostanes urinary levels (b) across quartiles of RTL.…”

Section: Discussionmentioning

confidence: 99%

“…Progressive attrition of telomeres leads to a critical length that triggers the cell arrest phenomenon known as senescence (Khan et al 2012), and due to the universal fact that telomere shorten with age, its study is crucial for understanding mechanisms of age-related diseases (Armanios 2013). Notably, it has been reported that telomere shortening and oxidative DNA damage in endothelial progenitor cells is higher in coronary artery disease patients with MetS than in those without MetS (Satoh et al 2008). In addition, endothelial damage and atherosclerosis have been shown to be associated with telomere shortening in white blood cells more tightly than chronological aging (Nakashima et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Influence of endothelial dysfunction on telomere length in subjects with metabolic syndrome: LIPGENE study

González-Guardia

Yubero‐Serrano

Rangel‐Zúñiga

et al. 2014

AGE

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Previous evidences support that increased oxidative stress (OxS) may play an important role in metabolic syndrome (MetS) and both are closely linked to vascular dysfunction. This study determined whether there is a relationship between endothelial function and relative telomere length (RTL) in MetS subjects. In this crosssectional study from the LIPGENE cohort, a total of 88 subjects (36 men and 52 women) were divided into four groups by quartiles of telomere length. We measured ischemic reactive hyperemia (IRH), total nitrite (NO) and protein carbonyl (PC) plasma levels, F2-isoprostanes urinary levels, and superoxide dismutase (SOD) and glutathione peroxidase (GPx) plasma activities. IRH and NO plasma levels were higher in subjects with longer RTL (quartiles 3 and 4), while PC plasma levels, F2-isoprostanes urinary levels, and GPx and SOD plasma activities were lower in quartile 4 subjects (longest RTL). Additionally, MetS subjects with longer RTL had greater homeostatic model assessment-β level and lower triglycerides plasma levels. Our results suggest that endothelial dysfunction, associated with high levels of OxS, could be entailed in an increment of telomere attrition. Thus, further support of the molecular and cellular mechanisms involved in vascular dysfunction may contribute to the development AGE (2014) 36:9681 DOI 10.1007/s11357-014-9681-9Lorena González-Guardia and Elena María Yubero-Serrano contributed equally to this work. Electronic supplementary material

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Association between oxidative DNA damage and telomere shortening in circulating endothelial progenitor cells obtained from metabolic syndrome patients with coronary artery disease

Cited by 134 publications

References 29 publications

Human aging and CD31⁺T-cell number, migration, apoptotic susceptibility, and telomere length

Human aging and CD31⁺T-cell number, migration, apoptotic susceptibility, and telomere length

MicroRNA‐216a induces endothelial senescence and inflammation via Smad3/IκBα pathway

Influence of endothelial dysfunction on telomere length in subjects with metabolic syndrome: LIPGENE study

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Association between oxidative DNA damage and telomere shortening in circulating endothelial progenitor cells obtained from metabolic syndrome patients with coronary artery disease

Cited by 134 publications

References 29 publications

Human aging and CD31+T-cell number, migration, apoptotic susceptibility, and telomere length

Human aging and CD31+T-cell number, migration, apoptotic susceptibility, and telomere length

MicroRNA‐216a induces endothelial senescence and inflammation via Smad3/IκBα pathway

Influence of endothelial dysfunction on telomere length in subjects with metabolic syndrome: LIPGENE study

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Human aging and CD31⁺T-cell number, migration, apoptotic susceptibility, and telomere length

Human aging and CD31⁺T-cell number, migration, apoptotic susceptibility, and telomere length