Cortistatin Inhibits Migration and Proliferation of Human Vascular Smooth Muscle Cells and Decreases Neointimal Formation on Carotid Artery Ligation

Rationale:Proliferation and migration of smooth muscle cells (SMCs) are key steps for the progression of atherosclerosis and restenosis. Cortistatin is a multifunctional neuropeptide belonging to the somatostatin family that exerts unique functions in the nervous and immune systems. Cortistatin is elevated in plasma of patients experiencing coronary heart disease and attenuates vascular calcification. Objective:To investigate the occurrence of vascular cortistatin and its effects on the proliferation and migration of SMCs in vitro and in vivo and to delimitate the receptors and signal transduction pathways governing its actions. Methods and Results:SMCs from mouse carotid and human aortic arteries and from human atherosclerotic plaques highly expressed cortistatin. Cortistatin expression positively correlated with the progression of arterial intima hyperplasia. Cortistatin inhibited platelet-derived growth factor–stimulated proliferation of human aortic SMCs via binding to somatostatin receptors (sst2 and...