Carvacrol inhibits atherosclerotic neointima formation by downregulating reactive oxygen species production in vascular smooth muscle cells

• Published in: Atherosclerosis 2015-06, Vol.240 (2), p.367-373
• Main Authors: Lee, Kang Pa, Sudjarwo, Giftania W, Jung, Seung Hyo, Lee, Donghyen, Lee, Dong-Youb, Lee, Gyoung Beom, Baek, Suji, Kim, Do-Yoon, Lee, Hwan Myung, Kim, Bokyung, Kwon, Seong-Chun, Won, Kyung Jong
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - pharmacology; Atherosclerosis - metabolism; Atherosclerosis - pathology; Atherosclerosis - prevention & control; Cardiovascular; Carotid Artery Injuries - drug therapy; Carotid Artery Injuries - metabolism; Carotid Artery Injuries - pathology; Carvacrol; Cell Movement - drug effects; Cell Proliferation - drug effects; Cells, Cultured; Disease Models, Animal; Dose-Response Relationship, Drug; Extracellular Signal-Regulated MAP Kinases - metabolism; Hydrogen Peroxide - metabolism; Male; Migration; Monoterpenes - pharmacology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - pathology; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; Myocytes, Smooth Muscle - pathology; NADH, NADPH Oxidoreductases - metabolism; NADPH Oxidase 1; Neointima; Neovascularization, Physiologic - drug effects; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation; Proliferating Cell Nuclear Antigen - metabolism; Proliferation; Proto-Oncogene Proteins c-sis - pharmacology; Rats, Sprague-Dawley; Reactive oxygen species; Reactive Oxygen Species - metabolism; Signal Transduction - drug effects; Vascular smooth muscle cells
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2015.03.038

Abstract Objective Carvacrol (2-methyl-5-(1-methylethyl) phenol), a cyclic monoterpene, exerts protective activities in a variety of pathological states including tumor growth, inflammation, and oxidative stress. However, it is unknown whether carvacrol affects events in vascular cells during the development of atherosclerotic neointima. We investigated the effects of carvacrol on the migration and proliferation of rat aortic smooth muscle cells (RASMCs) and on vascular neointima formation. Methods and results Carvacrol significantly inhibited platelet-derived growth factor (PDGF)-BB-stimulated RASMC migration and proliferation in a concentration-dependent manner. Cell viability was not affected by treatment with carvacrol. Carvacrol attenuated the expression of NADPH oxidase (NOX) 1 and the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase 1/2 in response to PDGF-BB. Moreover, carvacrol suppressed the PDGF-BB-stimulated generation of H2 O2 and inhibited the activity of NOX in RASMCs. Treatment with carvacrol inhibited PDGF-BB-induced aortic sprout outgrowth, balloon injury-evoked vascular neointima formation, and expression of proliferating cell nuclear antigen in the neointima. Conclusion These findings indicate that carvacrol inhibits migration and proliferation of RASMCs by suppressing the reactive oxygen species-mediated MAPK signaling pathway in these cells, thereby attenuating vascular neointimal formation. Carvacrol may be a promising agent for preventing vascular restenosis or atherosclerosis.