Scutellarin alleviates tensile stress-induced proliferation and migration of venous smooth muscle cells via mediating the p38 MAPK pathway

Objective: Abnormal proliferation and migration of biomechanical force-induced venous smooth muscle cells (VSMCs) is a major cause to limit the efficacy of coronary artery bypass grafting (CABG) for coronary heart disease (CHD). Scutellarin is the main active ingredient of Erigeron Breviscapus, and has broad-spectrum pharmacological effects. Therefore, the present study was proposed to investigate the effect of Scutellarin on VSMCs under tensile stress.

Methods: After interfering with VSMCs at different tensile stresses, the optimal tensile stress was screened. In a tensile stress environment, 100 μM Scutellarin and Hesperetin (p38 MAPK pathway activator) was used to treatment with VSMCs. CCK-8, EDU, Wound healing, flow cytometry and western blotting assays were used to detect cell proliferation, migration, Apoptosis, and the expression of apoptosis-related proteins (Caspase3, Bcl2 and Bax).

Results: Tensile stress with 10% significantly enhanced the activity, wound-healing ratio, and EDU+ cells of VSMCs, and decreased their Apoptosis ratio. Moreover, it upregulated Bcl2 expression, and downregulated cleaved-Caspase3 and Bax expression of VSMCs. Hence, 10% tensile stress was selected to creates a tensile stress environment for VSMCs. Interestingly, 100 μM Scutellarin alleviated the effect of 10% tensile stress on the phenotype of VSMCs. Notably, 10% tensile stress increased the phosphorylation level of p38 MAPK (Thr180 +Tyr182) in VSMCs, which was restricted by Scutellarin. Further, Hesperetin restored the effect of Scutellarin on the phenotype of VSMCs.

Conclusion: Scutellarin alleviates tension stress-induced proliferation and migration of VSMCs via suppressing p38 MAPK pathway. Scutellarin may be used as an adjunctive strategy for future GABG treatment in CHD patients.

Coronary heart disease; Neointimal hyperplasia; P38 MAPK pathway; Scutellarin; Tensile stress; Venous smooth muscle cells.