Emerging roles of SIRT1 in vascular endothelial homeostasis

Potente, Michael; Dimmeler, Stefanie

doi:10.4161/cc.7.14.6267

Cited by 145 publications

(108 citation statements)

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“…SIRT1 has been pointed as a key regulator of vascular endothelial homeostasis controlling angiogenesis, vascular tone and endothelial dysfunction [22]. More evidence has pointed out that SIRT1 is a key inducible factor in response to inflammatory stimulation.…”

Section: Discussionmentioning

confidence: 99%

SIRT1 suppresses PMA and ionomycin-induced ICAM-1 expression in endothelial cells

Jia

Gao

Chen

et al. 2012

Sci. China Life Sci.

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Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the recruitment of leukocytes to the endothelium, which causes inflammation and initiation of atherosclerosis. We have previously shown that endothelium-specific over-expression of class III deacetylase SIRT1 decreases atherosclerosis. We therefore addressed the hypothesis that SIRT1 suppresses ICAM-1 expression in the endothelial cells. Here, we found that expression of SIRT1 and ICAM-1 was significantly induced by PMA and ionomycin (PMA/Io) in human umbilical vein endothelial cells (HUVECs). Adenovirus-mediated over-expression of SIRT1 significantly inhibited PMA/Io-induced ICAM-1 expression in HUVECs. Knockdown of SIRT1 by RNA interference (RNAi) resulted in increased expression of ICAM-1 in HUVECs. Luciferase report assay showed that over-expression of SIRT1 suppressed ICAM-1 promoter activity both in basic and in PMA/Io-induced conditions. We further found that SIRT1 was involved in transcription complex binding on the ICAM-1 promoter by chromatin immunoprecipitation (ChIP) assays. Furthermore, SIRT1 RNAi increased NF-κB p65 binding ability to the ICAM-1 promoter by ChIP assays. Overall, these data suggests that SIRT1 inhibits ICAM-1 expression in endothelial cells, which may contribute to its anti-atherosclerosis effect. SIRT1, ICAM-1, PMA and ionomycin Citation:Jia Y Y, Gao P, Chen H Z, et al. SIRT1 suppresses PMA and ionomycin-induced ICAM-1 expression in endothelial cells .

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Section: Discussionmentioning

confidence: 99%

SIRT1 suppresses PMA and ionomycin-induced ICAM-1 expression in endothelial cells

Jia

Gao

Chen

et al. 2012

Sci. China Life Sci.

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“…SIRT1 promotes eNOS-dependent endothelial function, 41 an early marker for the development of hypertension in PT infants. 2,3,42 Arterial stiffness is also regulated by SIRT1 by preventing hyperphosphathemia-induced calcification.…”

Section: Discussionmentioning

confidence: 99%

Accelerated senescence of cord blood endothelial progenitor cells in premature neonates is driven by SIRT1 decreased expression

Vassallo

Simoncini

Ligi

et al. 2014

Blood

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Key Points• We demonstrate that PT promotes ECFCs dysfunction by inducing stress-induced premature senescence.• Our data reveal that SIRT1 deficiency drives PT-ECFC senescence, and acts as a critical determinant of the PT-ECFC angiogenic defect.Epidemiological and experimental studies indicate that early vascular dysfunction occurs in low-birth-weight subjects, especially preterm (PT) infants. We recently reported impaired angiogenic activity of endothelial colony-forming cells (ECFCs) in this condition. We hypothesized that ECFC dysfunction in PT might result from premature senescence and investigated the underlying mechanisms. Compared with ECFCs from term neonates (n 5 18), ECFCs isolated from PT (n 5 29) display an accelerated senescence sustained by growth arrest and increased senescence-associated b-galactosidase activity. Increased p16INK4a expression, in the absence of telomere shortening, indicates that premature PT-ECFC aging results from stress-induced senescence. SIRT1 level, a nicotinamide adenine dinucleotidedependent deacetylase with anti-aging activities, is dramatically decreased in PT-ECFCs and correlated with gestational age. SIRT1 deficiency is subsequent to epigenetic silencing of its promoter. Transient SIRT1 overexpression or chemical induction by resveratrol treatment reverses senescence phenotype, and rescues in vitro PT-ECFC angiogenic defect in a SIRT1-dependent manner. SIRT1 overexpression also restores PT-ECFC capacity for neovessel formation in vivo. We thus demonstrate that decreased expression of SIRT1 drives accelerated senescence of PT-ECFCs, and acts as a critical determinant of the PT-ECFC angiogenic defect. These findings lay new grounds for understanding the increased cardiovascular risk in individuals born prematurely and open perspectives for therapeutic strategy. (Blood. 2014;123(13):2116-2126

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“…2). In addition, SirT1 controls angiogenesis and vasculogenesis during development (Potente et al, 2007;Potente and Dimmeler, 2008); however, its regenerative potential in other tissues is unknown. This is an active field of investigation in skeletal and heart muscle diseases since these tissues were long considered 'post-mitotic' and therefore have a limited regenerative capacity upon aging, damage, skeletal muscle dystrophy or cardiac infarct.…”

Section: Perspectivementioning

confidence: 99%