Gdf-15 Promotes Proliferation Of Vascular Smooth Muscle Cells Through Mapk-Activated Protein Kinase Pathways

Growth differentiation factor 15 (GDF-15) is a multifunctional member of the TGF-b superfamily. Accumulating evidence indicates that GDF15 is an independent biomarker for the cardiovascular disease, and is closely involved in the development of atherosclerotic lesions induced by ox-LDL, such as inhibition of macrophage infiltration and increase of endothelial cell proliferation, while whether GDF-15 also participates into the VSMCs proliferation is still lack of systemic analysis. In the present study, ox-LDL was found to induce GDF15 expression and secretion in cultured rat VSMCs in a p38- and ERK1/2-dependent manner. Inhibition of ox-LDL-induced GDF-15 expression by siRNA transfection by lentivirus demonstrated that adaptively induced GDF15 played a proliferative role in VSMCs, and overexpression of GDF-15 alone was adequate to induce VSMCs proliferation. Further application of inhibitors of p38- and ERK1/2 attenuated the GDF-15 expression induced by ox-LDL. All data suggest that GDF15 is a proliferative molecule that gives rise to VSMCs proliferation secondary to ox-LDL stimulation in vitro.