Inhibition of neointima hyperplasia by the combined therapy of linagliptin and metformin via AMPK/Nox4 signaling in diabetic rats
Abstract
Neointima hyperplasia is the pathological basis of atherosclerosis and restenosis which have been associated with diabetes mellitus (DM). It is controversial for linagliptin and metformin to protect against vascular neointimal hyperplasia caused by DM. Given the combined therapy of linagliptin and metformin in clinical practice, we investigated whether the combination therapy inhibited neointimal hyperplasia in the carotid artery in diabetic rats. Neointima hyperplasia in the carotid artery was induced by balloon-injury in the rats fed with high fat diet (HFD) combined with low dose streptozotocin (STZ) administration. In vitro, vascular smooth muscle cells (VSMCs) were incubated with high glucose (HG, 30 mM) and the proliferation, migration, apoptosis and collagen deposition were analyzed in VSMCs. We found that the combined therapy, not the monotherapy of linagliptin and metformin significantly inhibited the neointima hyperplasia and improved the endothelium-independent contraction in the balloon-injured cardia artery of diabetic rats, which was associated with the inhibition of superoxide (O2-.) production in the cardia artery. In vitro, HG-induced VSMC remodeling was shown as the remarkable upregulation of PCNA, collagan1, ...Continue Reading
References
Complex regulation and function of the inflammatory smooth muscle cell phenotype in atherosclerosis.
Linagliptin plus metformin in patients with newly diagnosed type 2 diabetes and marked hyperglycemia
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