The role of the receptor of advanced glycosylation end products in apoptosis of human coronary endotheli-al cells induced by intermittent high glucose
Objective We found that intermittent high glucose in diabetic patients was easy to suffer from coronary athero-sclerosis.To explore the mechanism,we investigated the apoptosis of human coronary endothelial cells in the context of persistent and fluctuating hyperglycemia,and explored whether apoptosis was mediated by the receptor of advanced glycosylation end products.Methods The HCAECs of logarithmic growth period were divided into 4 groups:①normal blood glucose group(CNG,5mmol/L glu-cose);②constant high glucose group(CHG,20 mmol/L glucose);③intermittent high glucose group(IHG,5mmol/L and 20 mmol/L glucose fluctuated every 8 h);④ intermittent mannitol control group(IM,5 mmol/L and 20 mmol/L mannitol fluctuated every 8 h,main-taining the same fluctuating osmotic pressure environment as intermit-tent high glucose).HCAECs treated under different conditions were selected.Cell viability was determined by MTT assays.The apoptosis of HCAECs was detected by flow cytometry.Protein levels of Caspase-3 and RAGE were detected by Western blotting,and transcription lev-els of RAGE were detected by qRT-PCR.The expression quantity of RAGE in HCAECs was knockdown by shRNA using lentivirus trans-fection.The expression of Caspase-3 in IHG was observed.Results Compared with the CNG group,the cell viability of the constant high glucose group(CHG)and the intermittent high glucose group(IHG)was decreased(P<0.05),but the cell viability of the IHG group was lower(P=0.035).The apoptosis rate(P=0.028),Caspase-3 activation(P=0.037)and RAGE expression were significantly increased in IHG group(P<0.05).Finally,we knocked down the RAGE expression level and found that the apoptosis of HCAECs induced by intermittent high glucose was significantly improved(P<0.05).Conclusion Intermittent high glucose can promote apoptosis and damage HCAECs by enhancing RAGE expression.
intermittent high glucosethe receptor of advanced glycation end productshuman coronary artery endothelial cellsapoptosis
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