Resistin-Like Molecule alpha Enhances the Proliferation and Migration of Aortic Vascular Smooth Muscle Cells

Abstract

Objective: The mitogenic and chemotactic effects of resistin-like molecule alpha (RELMα) are thought to contribute to vascular remodeling in pulmonary arterial hypertension. Here we evaluate the expression of RELMα in atherosclerotic plaque and investigate its effects on the proliferation and migration of vascular smooth muscle cells (VSMCs). Methods: An atherosclerotic model was established by feeding 4-week-old C57BL/6J ApoE-/- mice (n = 9) with a high-fat diet. Wild-type 4-week-old C57BL/6J (n = 9) were fed the same diet and were used as controls. RELMα expression wasevaluated by immunohistochemistry and quantified using real-time PCR (RT-PCR). A ³H-thymidine incorporation assay and the Boyden chamber assay, respectively, were used to explore the effects of different concentrations of RELMα on the proliferation and migration of VSMCs. Results: Immunohistochemistry identified positively stained granules in atherosclerotic plaques. These results were confirmed by detection of RELMα mRNA using RT-PCR. We also demonstrated that in vitro exposure to RELMα significantly promoted the proliferation and migration of VSMCs in a dose-related manner (p < 0.01). Conclusions: RELMα expressed in atherosclerotic plaque of ApoE-/- mice appears to enhance the proliferation and migration of aortic VSMCs in a dose-related manner.

Resistin-like molecules: a marker, mediator and therapeutic target for multiple diseases

“…RELMα and RELMβ plays an importance role in the pathology of atherosclerosis. RELMα is up-regulated in atherosclerotic plaque of ApoE −/− mice [ 102 ]. Importantly, RELMα dramatically enhances the proliferation and migration of VSMCs [ 102 ].…”

“…RELMα is up-regulated in atherosclerotic plaque of ApoE −/− mice [ 102 ]. Importantly, RELMα dramatically enhances the proliferation and migration of VSMCs [ 102 ]. It has been demonstrated that RELMα ameliorates HFD-induced hypercholesterolaemia and atherosclerosis by promoting the conversion of cholesterol into bile acids and mediating its subsequent fecal excretion via liver receptor homologue-1 (Lrh-1)-induced enhancement of hepatic cholesterol 7α-hydroxylase (CYP7A1) gene transcription [ 20 ].…”