Effect of the antioxidant α-lipoic acid on apoptosis in human umbilical vein endothelial cells induced by high glucose

Abstract

High glucose plays an important role in the pathogenesis of atherosclerosis. In this study, we assessed the effects of high glucose on human umbilical vein endothelial cell (HUVEC) apoptosis. Additionally, we investigated whether alpha-lipoic acid, an antioxidant, prevents high glucose-induced apoptosis of HUVECs. HUVECs were treated with high glucose in the presence or absence of alpha-lipoic acid. Treatment of HUVECs with high glucose changed cell morphology and induced DNA fragmentation, leading to apoptosis. Apoptosis was induced by high glucose in a dose-and time-dependent fashion. High glucose markedly elevated Bax, and decreased NF-kappaB and Bcl-2 expression. Most importantly, pretreatment with alpha-lipoic acid protected against high glucose-induced apoptosis in the endothelial cells. alpha-Lipoic acid significantly promoted the expression of NF-kappaB while decreasing the expression of Bax and the activities of caspase-3 and-9 without significantly affecting the Bcl-2 level. Our data suggest that high glucose induces apoptosis in endothelial cells. alpha-Lipoic acid effectively attenuates high glucose-induced endothelial cell apoptosis. These findings provide new perspectives on the role of alpha-lipoic acid in cardiovascular disease.

Insulin-like growth factor-1 receptor activation prevents hydrogen peroxide-induced oxidative stress, mitochondrial dysfunction and apoptosis

“…The principal mediator of oxidative stress-dependent signaling is hydrogen peroxide (H 2 O 2 ) [1], and H 2 O 2 -induced endothelial apoptosis further complicate the pathogenesis of vascular disease [2][3][4]. The cytotoxic actions of H 2 O 2 are complicated, and perhaps mediated, in part, through mitochondria [2,[5][6][7][8]. As a source of reactive oxygen species (ROS) and a sensor of oxidative stress [9,10], mitochondria play a key role in regulation of apoptosis under a variety of pathological conditions, including ischemia, hypoxia, and myocardial infarction [11][12][13][14].…”

“…The principal mediator of oxidative stress-dependent signaling is hydrogen peroxide (H 2 O 2 ) [1], and H 2 O 2 -induced endothelial apoptosis further complicate the pathogenesis of vascular disease [2][3][4]. The cytotoxic actions of H 2 O 2 are complicated, and perhaps mediated, in part, through mitochondria [2,[5][6][7][8].…”

Mononuclear Cell Transcriptome Response after Sustained Virgin Olive Oil Consumption in Humans: An Exploratory Nutrigenomics Study

“…Both the oxidized and reduced forms of LA are antioxidants (Bast and Haenen, 2003;Moini et al, 2002). LA effectively attenuates high glucose-induced endothelial cell apoptosis, which could explain a role of LA in CVD (Meng et al, 2008). A dietary LA supplementation inhibits the atherosclerotic lesion formation in mouse models of human atherosclerosis due to its anti-inflammatory, antihypertriglyceridemic, and weight-reducing effects, and therefore, may be a useful tool in the prevention and treatment of atherosclerotic vascular diseases .…”

Erectile Dysfunction Complicating Cardiovascular Risk Factors and Disease

“…(The reader is referred to standard vascular texts for the pathology of atherosclerosis) The ensuing diffuse atherosclerosis and micro-angiopathy is responsible for the nephropathy, retinopathy, stroke, coronary artery disease and ED that accompany DM. According to Meng et al, 57 higher glucose levels induces apoptosis in endothelial cells while Di Filippo et al 58 conclude that DM is associated with increased cardiovasular disease due to established risk factors such as dyslipdemia , hypertension and atherosclerosis as a result of increased inflammation. This leads to the production of free oxygen radicals, impaired NO metabolism and increased movement of lipids into the intima leading to early and diffuse atherosclerosis.…”