Abstract
Advanced glycation end products (AGEs) have been widely regarded as an important inducing factor in the pathogenesis of diabetic arteriosclerosis, and the proliferation and migration of vascular smooth muscle cells (VSMCs) are also involved in this process. However, it is not clear whether AGEs promote atherosclerosis by inducing the proliferation and migration of VSMCs. To figure out this question, this study investigated the effects of AGEs on the proliferation and migration of human aorta vascular smooth muscle cells (HASMCs) and the underlying mechanisms. This study evaluated the effects of different concentrations of AGEs on cell proliferation and migration. CCK8, transwell, and western blotting assays demonstrated that AGEs significantly increased cell proliferation and migration in a concentration-dependent manner and that the optimal proproliferative and promigratory concentrations of AGEs were 10 mg/L and 20 mg/L, respectively. AGE-induced cell proliferation, migration, and expression of filament actin (F-actin) were markedly attenuated by a PI3K inhibitor (LY2940002). Additionally, the phosphorylation of AKT was reduced when the receptor of advanced glycation end product (RAGE) gene was silenced by lentivirus transfection, which led to a concomitant reduction of the expression of proliferation and migration-related proteins. These data indicate that AGEs may activate the PI3K/AKT pathway through RAGE and thus facilitate the proliferation and migration of HASMCs.
Highlights
Diabetes mellitus (DM) is a major cardiovascular risk factor and is associated with increased cardiovascular events and mortality
The immunofluorescence imaging (Figure 1) revealed that the human aorta vascular smooth muscle cells (HASMCs) expressed α-SMA, as the positive green fluorescence was emitted from the cytoplasm of the cells
CCK8 assay showed that, after HASMCs were treated with Advanced glycation end products (AGEs), the proliferation ability of cells was significantly enhanced, compared with control cells, in a concentrationdependent manner, and cell proliferation ability was the strongest when AGE concentration was 10 mg/L (Figure 2(a))
Summary
Diabetes mellitus (DM) is a major cardiovascular risk factor and is associated with increased cardiovascular events and mortality. Atherosclerosis (AS) is one of the most common vascular complications of diabetes mellitus and a leading cause of death and disabling cardiovascular disease [1, 2]. The underlying mechanisms of diabetic atherosclerosis can be attributed to a combination of factors, including oxidative stress, inflammation, increased expression of growth factors, and increased production of AGEs [3, 4]. AGEs are the products of nonenzymatic glycosylation and oxidation of a group of proteins and lipids after continuous contact with reducing sugars or short-chain aldehydes. They are common in the vasculature of diabetic patients, accelerating the development of AS.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
