Prostaglandin E1 Inhibited Diabetes-Induced Phenotypic Switching of Vascular Smooth Muscle Cells Through Activating Autophagy

Abstract

Background/Aims: The phenotype switching of vascular smooth muscle cells (VSMCs) was associated with the onset or progression of the atherogenic process in type 2 diabetes mellitus (T2DM). Alprostadil (Prostaglandin E1, PGE1) as a bioactive drug had a protective effect on vascular function. However, it is unknown whether PGE1 inhibited the phenotype switching in VSMCs via autophagy, which played a protective role in the vascular complications of diabetes. Methods: The phenotype switching was induced by high glucose (HG, 25mM) in VSMCs, the protein expression was measured by western blot analysis and immunofluorescent staining. In vivo study, vascular lesion and dysfunction were produced in the rats fed with high fat diet (HFD) combined with low dose streptozotocin (STZ) administration. Results: The decrease of α-SMA and the increase of vimentin, collagen I and proliferating cell nuclear antigen (PCNA) were found in HG-treated VSMCs. Along with more abundance of p62, autophagy markers LC3B and Beclin-1 significantly decreased in VSMCs exposed to HG. Such abnormal changes were significantly reversed by PGE1, which mimicked the role of autophagy activator rapamycin and was dramatically counteracted by 3-methyladenine, an autophagy inhibitor. Furthermore, PGE1 suppressed the phosphorylation of AKT and mTOR, which negatively regulated autophagy level in VSMCs. In vivo study, PGE1 remarkably improved the endothelium-independent contraction of thoracic aorta and restored the expression of α-SMA, osteopontin, LC3B, phosphorylated mTOR in the artery media of T2DM rats. Conclusion: These results demonstrated that PGE1 maintained the phenotype of VSMCs via the AKT/mTOR-dependent autophagy, which prevented diabetes-induced vascular complications.

BGP-15 Inhibits Hyperglycemia-Aggravated VSMC Calcification Induced by High Phosphate

“…In diabetic rat carotid arteries, expression of smooth muscle-specific markers including ACTA, myosin heavy chain, and calponin-1 is significantly decreased [45]. Others also have found that contractile smooth muscle-specific markers are decreased in response to hyperglycemia [46]. Along the lines with these results, we showed that both high Pi and HG triggered the loss of SMC-specific markers, and the HG condition aggravated high Pi-induced downregulation of SMC markers.…”

Autophagy as a novel therapeutic target in vascular calcification

“…Recent studies have shown that autophagy induction inhibits both the endothelial dysfunction (Fetterman, et al, 2016;Y. Xie, et al, 2011) in endothelial cells from diabetic patients and phenotypic switching of VSMCs in diabetic vascular lesions (An, Li, Wei, Li, & Xu, 2018;Qiu, et al, 2018). These studies demonstrate a protective role of autophagy in diabetic vascular disorders.…”

Hengshun Aromatic Vinegar Improves Glycolipid Metabolism in Type 2 Diabetes Mellitus via Regulating PGC-1α/PGC-1β Pathway

“…Initially, rats were randomly divided into two groups: HFD group and normal diet group. Rats in HFD group were fed HFD for 4 weeks, and then given an intraperitoneal injection of a single dose of STZ (40 mg/kg) (dissolved in citrate buffer at pH 4.5, Saiguo Biotechnology, Guangzhou, China) to induce T2DM (An et al, 2018). Rats in normal diet group were fed chow diet for the same period, and given an intraperitoneal injection of citrate buffer.…”