Apoptosis in the vasculature: mechanisms and functional importance

Mallat, Ziad; Tedgui, Alain

doi:10.1038/sj.bjp.0703407

Cited by 307 publications

(230 citation statements)

References 154 publications

(177 reference statements)

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“…Several in vitro studies have demonstrated that a variety of stimuli can induce programmed cell death (apoptosis) in endothelial cells (1,2), and anomalous endothelial cell apoptosis has been considered a common feature in numerous cardiovascular diseases such as atherosclerosis, hypertension, and diabetes (3)(4)(5)(6)(7)(8). Endothelial cell death leads to vascular leak and exposes the flowing bloodstream to the potently thrombogenic subendothelial matrix.…”

mentioning

confidence: 99%

Activation of AMP-activated Protein Kinase α1 Alleviates Endothelial Cell Apoptosis by Increasing the Expression of Anti-apoptotic Proteins Bcl-2 and Survivin

Liu

Liang

Wang

et al. 2010

Journal of Biological Chemistry

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Accumulating evidence suggests that AMP-activated protein kinase (AMPK) activation exerts anti-apoptotic effects in multiple types of cells. However, the underlying mechanisms remain poorly defined. The aim of the present study was to determine how AMPK suppresses apoptosis in endothelial cells exposed to hypoxia and glucose deprivation (OGD). AMPK activity, NF-B activation, and endothelial cell apoptosis were assayed in cultured endothelial cells and mouse common carotid artery with or without OGD treatment. OGD markedly activated AMPK as early as 30 min, and AMPK activity reached maximal at 2 h of OGD. Endothelial apoptosis was not detected until 2 h of OGD but became markedly elevated at 6 h of OGD treatment. Furthermore, AMPK inhibition by Compound C or overexpression of dominant negative AMPK (AMPK-DN) exacerbated, whereas AMPK activation by pharmacologic (aminoimidazole carboxamide ribonucleotide (AICAR)) or genetic means (overexpression of constitutively active AMPK) suppressed endothelial cell apoptosis caused by OGD. Concomitantly, AMPK activation increased the expression of both Bcl-2 and Survivin, two potent anti-apoptotic proteins. Furthermore, AMPK activation significantly enhanced IB␣ kinase activation, NF-B nuclear translocation, and DNA binding activity of NF-B. Consistently, selective inhibition of NF-B, which abolished OGD-enhanced expression of Bcl-2 and Survivin, accentuated endothelial apoptosis caused by OGD. Finally, we found that genetic deletion of the AMPK␣1, but not AMPK␣2, suppressed OGD-enhanced NF-B activation, the expression of Bcl-2 and Survivin, and endothelial apoptosis. Overall, our results suggest that AMPK␣1, but not AMPK␣2 activation, promotes cell survival by increasing NF-B-mediated expression of anti-apoptotic proteins (Bcl-2 and Survivin) and intracellular ATP contents.

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mentioning

confidence: 99%

Activation of AMP-activated Protein Kinase α1 Alleviates Endothelial Cell Apoptosis by Increasing the Expression of Anti-apoptotic Proteins Bcl-2 and Survivin

Liu

Liang

Wang

et al. 2010

Journal of Biological Chemistry

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“…It is well-established that apoptosis can be induced by internal signals, such as cytochrome C and apoptosis-inducing factors released from mitochondria, and that it is commonly associated with decreases in mitochondrial membrane potential and ATP production (14 -16). In addition, such factors as caspases, ceramide, and oxidative stress have been implicated in its causation, whereas other factors, including shear stress, IGF-I, insulin, and Akt activation, have been shown to be antiapoptotic (17)(18)(19)(20)(21). Despite this, the metabolic mechanism(s) by which hyperglycemia initiates apoptosis in endothelium is incompletely understood.…”

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confidence: 98%

Hyperglycemia-Induced Apoptosis in Human Umbilical Vein Endothelial Cells

Carling²,

2002

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Apoptosis has been observed in vascular cells, nerve, and myocardium of diabetic humans and experimental animals, although whether it contributes to or is a marker of complications in these tissues is unclear. Previous studies have shown that incubation of human umbilical vein endothelial cells (HUVECs) with 30 vs. 5 mmol/l glucose for 72 h causes a significant increase in apoptosis, possibly related to an increase in oxidative stress. We report here that this increase in apoptosis (assessed morphologically by TdT-mediated dUTP nickend labeling staining) is preceded (24 h of incubation) by inhibition of fatty acid oxidation, by increases in diacylglycerol synthesis, the concentration of malonyl CoA, and caspase-3 activity, and by decreases in mitochondrial membrane potential and cellular ATP content. In addition, the phosphorylation of Akt in the presence of 150 U/ml insulin was impaired. No increases in ceramide content or its de novo synthesis were observed. AMP-activated protein kinase (AMPK) activity was not diminished; however, incubation with the AMPK activator 5-aminoimidazole-4-carboxamideriboside increased AMPK activity twofold and completely prevented all of these changes. Likewise, expression of a constitutively active AMPK in HUVEC prevented the increase in caspase-3 activity. The results indicate that alterations in fatty-acid metabolism, impaired Akt activation by insulin, and increased caspase-3 activity precede visible evidence of apoptosis in HUVEC incubated in a hyperglycemic medium. They also suggest that AMPK could play an important role in protecting the endothelial cell against the adverse effects of sustained hyperglycemia. Diabetes 51:159 -167, 2002 V ascular disease that affects both the micro-and macrovasculature is the principal cause of morbidity and mortality in patients with diabetes (1). A wide variety of studies suggest that an early site at which these vascular complications develop is the endothelium. In particular, early abnormalities such as increases in renal and retinal blood flow, impaired vasodilation in response to physiological and pharmacological stimuli, and increased vascular permeability have been attributed to endothelial cell damage (1). Morphological correlates of these functional abnormalities were not initially identified; however, recent studies have shown an increase in apoptosis in various organs affected by diabetes, including the eye (2,3), heart (4,5), and vascular endothelium (5).The Diabetes Control and Complications Trial (6) and the U.K. Prospective Diabetes Study (7,8) have linked hyperglycemia to the occurrence of microvascular disease in patients with diabetes. Although less clear-cut, a relationship between hyperglycemia and macrovascular disease (9) has also been reported. That hyperglycemia increases apoptosis in cultured endothelium was first demonstrated by in HUVECs and since then by many others (11-13). It is well-established that apoptosis can be induced by internal signals, such as cytochrome C and apoptosis-inducing factors released from ...

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“…VSMCs, the main structure of artery medium layer, also play a significant role on the formation of advanced stage of atherosclerosis. Apoptosis of VSMCs is harmful to the stability of atherosclerosis plaque [42]. Therefore, maintenance of VSMCs has potential to delay the progression of atherosclerosis [31].…”

Section: Let-7g and Apoptosismentioning

confidence: 99%

MicroRNA Let-7g and Atherosclerosis Plaque Stabilization

Yin¹,

Zhang²,

Hou³

et al. 2017

WJCD

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Vascular atherosclerotic vulnerable plaque rupture is the primary cause of acute myocardial infarctions and strokes. Thus, stabilization of vulnerable plaques is of important clinical endeavor to decrease the fatal risk of atherosclerosis. Inflammatory infiltration, apoptosis of endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), destruction of extracellular matrix (ECM) or collagen, and neovascularization all contribute to the formation and stability of plaque. Let-7g, one miRNA of let-7 family, is related to retardation of the progress of vulnerable atherosclerosis plaque. First of all, let-7g induced preservation on vascular diseases through regulating on the intracellular Ca 2+ -activated protein kinase C-oxLDL-LOX-1 pathway, which resulted in reduced leukocyte adhesion to and migration across endothelium. Over expression of let-7g negatively regulated apoptosis in the ECs by targeting lectin-like oxidized LDL receptor-1(LOX-1)/CASP3 expression, therefore made the fibrous cap of plaque integrated and thick, increased the density of vascular atherosclerotic plaque. In addition, let-7g might stabilize the atherosclerotic plaque through other aspects. In this review, we focus on current and potential importance of let-7g on the stabilization of atherosclerosis plaque which might lead to the future development of an alternative strategy of CAD.

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Apoptosis in the vasculature: mechanisms and functional importance

Cited by 307 publications

References 154 publications

Activation of AMP-activated Protein Kinase α1 Alleviates Endothelial Cell Apoptosis by Increasing the Expression of Anti-apoptotic Proteins Bcl-2 and Survivin

Activation of AMP-activated Protein Kinase α1 Alleviates Endothelial Cell Apoptosis by Increasing the Expression of Anti-apoptotic Proteins Bcl-2 and Survivin

Hyperglycemia-Induced Apoptosis in Human Umbilical Vein Endothelial Cells

MicroRNA Let-7g and Atherosclerosis Plaque Stabilization

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