SIRT1 reduces endothelial activation without affecting vascular function in ApoE-/- mice

Stein, Sokrates; Schäfer, Nicola; Berndt, Alexander; Besler, Christian; Winnik, Stephan; Lohmann, Christine; Heinrich, Kathrin; Brokopp, Chad E.; Handschin, Christoph; Landmesser, Ulf; Tanner, Felix C.; Lüscher, Thomas F.; Matter, Christian M.

doi:10.18632/aging.100162

Cited by 142 publications

(116 citation statements)

References 27 publications

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“…It suggests that SIRT1 has a compensatory upregulation in endothelial cells in response to inflammatory factors. Moreover, expression of ICAM-1 was found to be increased in atherosclerotic plaques of ApoE / SIRT1 +/ mice compared with ApoE / SIRT1 +/+ mice [17]. Furthermore, we demonstrated that SIRT1 significantly inhibited PMA/Io-induced ICAM-1 expression in HUVECs to 50%.…”

Section: Discussionmentioning

confidence: 61%

“…We have previously shown that transgenic mice that overexpress SIRT1 in the vascular endothelium have better endothelium-dependent vasodilation and fewer atherosclerotic lesions when fed a high-fat diet [16]. Recently, expression of ICAM-1 was increased in atherosclerotic plaques of ApoE / SIRT1 +/ compared with ApoE / SIRT1 +/+ mice [17]. However, the mechanism by which SIRT1 regulates ICAM-1 expression remains unknown.…”

mentioning

confidence: 99%

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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: 61%

mentioning

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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“…So, in the vasculature, SIRT1 gain-of-function using SIRT1 overexpression has been shown to improve endothelial function in mice. Subsequently, it was described that SIRT1 does not directly inluence endothelium-dependent vascular function in ApoE−/− mice, but it improves vascular function by preventing superoxide production in ECs and reduces the expression of inlammatory adhesion molecules by suppressing NF-κB signalling [58].…”

Section: Atherosclerosismentioning

confidence: 99%

Angiogenesis and Cardiovascular Diseases: The Emerging Role of HDACs

Moraga¹,

Lao²,

Zeng³

2017

Physiologic and Pathologic Angiogenesis - Signaling Mechanisms and Targeted Therapy

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Cardiovascular diseases (CVD) continue to be the leading cause of death in the world despite recent therapeutic advances. Although many CVDs remain incurable, enormous eforts have been placed in harnessing angiogenesis as therapeutics for these diseases. Epigenetics, the modiication of gene expression post-transcriptionally and post-translationally, are important in regulating many biological processes. One of the main post-translational epigenetic modiications, modiication of chromatin structure by the acetylation of histone tails within the chromatin by either histone deacetylases (HDACs) or histone acetyltransferases (HATs), is important in modulating gene transcription and has emerged as an important regulatory player from pathogenesis to therapeutics in CVDs. Particularly, HDACs, which are largely involved in promoting chromatin compaction and hence inhibitions of gene transcription, have been implicated in the pathogenic signalling underlying many aspects of CVDs. Recently, histone modiications have been demonstrated to play important roles in the angiogenesis process. Pharmacological inhibitions of HDACs have displayed promising therapeutic potentials in several pre-clinical models of CVDs where angiogenesis is of paramount importance. There are many evidences proving that pro-and anti-angiogenic therapies-and the impact of epigenetics in these processes-can help to artiicially reconstruct the vasculature in patients with cardiovascular diseases. Conversely, utilising knowledge of HDACs in angiogenesis might help to develop anti-angiogenic therapies in tackling diseases that are characterised with excessive pathological angiogenesis, including cancer and age-related macular degeneration. Understanding the molecular mechanisms underlying HDACs in modulating angiogenesis will undoubtedly beneit future therapeutics development. This chapter focuses on the emerging role of HDACs in angiogenesis and discuss their potentials and challenges in utilising HDAC inhibitors as therapeutics in several major cardiovascular diseases.

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“…Потаскалова запалення через інгібування сигналів NF-κB і зниження рівня експресії ICAM-1 і VCAM-1. Доведено, що ресвератрол підвищує актив-ність eNOS і підтримує нормальну функцію ендотелію [48].…”

Section: можливості профілактики та лікування аг через епігенетичні вunclassified

Epigenetics of Arterial Hypertension

2017

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SIRT1 reduces endothelial activation without affecting vascular function in ApoE-/- mice

Cited by 142 publications

References 27 publications

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

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

Angiogenesis and Cardiovascular Diseases: The Emerging Role of HDACs

Epigenetics of Arterial Hypertension

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