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Ramipril protects the endothelium from hyperglycaemia‐induced dysfunction through AMPK and HO‐1 activation (851.10)
Author(s) -
Tian Shiliu,
Liu Yu,
Ge Xinfa,
Wu Ke,
Yang Huabing
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.851.10
Subject(s) - ramipril , endothelial dysfunction , ampk , oxidative stress , endocrinology , endothelium , vasodilation , medicine , diabetes mellitus , glycation , chemistry , pharmacology , enzyme , biochemistry , protein kinase a , blood pressure
Aims : To investigate the effects of ramipril (RPL), an angiotensin‐converting enzyme (ACE) inhibitor, on endothelial dysfunction associated with diabetes mellitus using cultured human aortic endothelial cells (HAECs) and a type 2 diabetic animal model. Methods and results : The effect of RPL on vasodilatory function in fat‐fed, streptozotocin‐treated rats was assessed. RPL treatment for 16 weeks starting at 8 weeks attenuated the decrease in endothelium‐dependent vasodilation in diabetic rats. RPL treatment also reduced serum advanced glycation end products (AGEs) concentration. Exposure of HAECs to high concentrations of glucose induced prolonged oxidative stress, apoptosis and accumulation of AGEs in HAEC. These effects were abolished by RPL incubation. In addition, RPL increased nuclear factor erythroid 2‐related factor‐2 (Nrf‐2) activation in a CaMKKβ/AMPK pathway dependent manner. RPL treatment increased the expression of the Nrf‐2‐regulated antioxidant enzyme, heme oxygenase‐1 (HO‐1). Conclusion: Ramipril ameliorates endothelial dysfunction in diabetes by enhancing vasodilation in addition to reducing oxidative stress. These effects are mediated by ramipril activation of CaMKK‐β, which in turn activates the AMPK‐Nrf‐2‐HO‐1 pathway for enhanced endothelial function. Grant Funding Source : Supported by Shanghai Key Laboratory of Human Performance(SUS) 11DZ2261100