High glucose induces cell death of cultured human aortic smooth muscle cells through the formation of hydrogen peroxide

Abstract

1 Alterations of the vessel structure, which is mainly determined by smooth muscle cells through cell growth and/or cell death mechanisms, are characteristic of diabetes complications. We analysed the in¯uence of high glucose (22 mM) on cultured human aortic smooth muscle cell growth and death, as hyperglycaemia is considered one of the main factors involved in diabetic vasculopathy. 2 Growth curves were performed over 96 h in medium containing 0.5% foetal calf serum. Cell number increased by 2 ± 4 fold over the culture period in the presence of 5.5 mM (low) glucose, while a 20% reduction in ®nal cell number was observed with high glucose. Under serum-free conditions, cell number remained constant in low glucose cultures, but a 40% decrease was observed in high glucose cultures, suggesting that high glucose may induce increased cell death rather than reduced proliferation. Reduced ®nal cell number induced by high glucose was also observed after stimulation with 5 or 10% foetal calf serum. 3 The possible participation of oxidative stress was investigated by co-incubating high glucose with di erent reactive oxygen species scavengers. Only catalase reversed the e ect of high glucose. Intracellular H 2 O 2 content, visualized with 2',7'-dichloro¯uorescein and quanti®ed by¯ow cytometry, was increased after high glucose treatment. 4 To investigate the cell death mechanism induced by high glucose, apoptosis and necrosis were quanti®ed. No di erences were observed regarding the apoptotic index between low and high glucose cultures, but lactate dehydrogenase activity was increased in high glucose cultures. 5 In conclusion, high glucose promotes necrotic cell death through H 2 O 2 formation, which may participate in the development of diabetic vasculopathy. British Journal of Pharmacology (2001) 133, 967 ± 974

Contribution of Aldose Reductase to Diabetic Hyperproliferation of Vascular Smooth Muscle Cells

“…Although previous reports demonstrated increased intimal thickening after balloon injury in alloxaninduced diabetic rabbits (27) and BB Wistar diabetic rats (28), recent studies report exaggerated intimal expansion in obese Zucker rats (29) but not in rats with STZ-induced diabetes (29,30). Coupled with the observation that in some studies, high glucose failed to stimulate SMC proliferation in culture (31,32), it is currently believed that hyperglycemia per se does not stimulate intimal hyperplasia in injured vessels and that insulin resistance or hyperinsulineima is responsible for the increased propensity of human diabetic patients for restenosis. This view is further reinforced by studies (33,34) showing that although rigorous control of hyperglycemia significantly decreases the microvascular complications such as nephropathy and retinopathy, it does not affect macrovascular complications of diabetes.…”

TUNEL-positive cells in the surgical border of an amputation due to infected diabetic foot

“…Apoptosis during acute complications of a chronic condition such as diabetic foot may be explained by at least 5 mechanisms: high glucose concentration (27)(28)(29)(30)(31), ketoacidosis, systemic inflammatory response (32), infection and hypoxia. The observation of apoptotic cells in the surgical borders may not have any clinical implication since it may be limited after the metabolic alterations and infection are controlled.…”

A high glucose condition sensitizes human hepatocytes to hydrogen peroxide-induced cell death

“…Several mechanisms of cell death in response to hydrogen oxide have been proposed (34)(35)(36)(37)(38). Of these, Peiro et al reported that a high concentration of hydrogen oxide induces necrosis and a low one apoptosis in human aortic smooth muscle cells (38).…”