phenylhydrazonopyrazolone-sulfonate-1 and Aortic-Diseases

Smooth muscle cells play an important role in the development of atherosclerosis. SHP2 is known to regulate the proliferation and migration of smooth muscle cells. The purpose of this study was to determine whether the SHP2 inhibitor PHPS1 has a pro-atherosclerotic or an atheroprotective effect in vivo and in vitro.. After exposure to a high-cholesterol diet for 4 weeks, LDL receptor-deficient (Ldlr. PHPS1 decreased the number of atherosclerotic plaques without significantly affecting body weight, serum glucose levels or lipid metabolism. Plaque composition analysis showed a significant decrease in the number of VSMCs in atherosclerotic lesions of Ldlr. The SHP2 inhibitor PHPS1 exerts a protective effect against atherosclerosis by reducing VSMC proliferation via SHP2/ERK pathway activation.

Topics: Animals; Aorta; Aortic Diseases; Atherosclerosis; Benzenesulfonates; Cell Proliferation; Cells, Cultured; Diet, High-Fat; Disease Models, Animal; Enzyme Inhibitors; Extracellular Signal-Regulated MAP Kinases; Hydrazones; Mice, Knockout; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Phosphorylation; Plaque, Atherosclerotic; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Receptors, LDL; Signal Transduction