title: Carvacrol inhibits atherosclerotic neointima formation by downregulating reactive oxygen species production in vascular smooth muscle cells.
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.
  
  
  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 H2O2 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Physiology, School of Medicine, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, South Korea.
authors: Kang Pa
authors: KP
authors: Lee
authors: Department of Physiology, School of Medicine, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, South Korea.
authors: Giftania W
authors: GW
authors: Sudjarwo
authors: Department of Physiology, School of Medicine, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, South Korea.
authors: Seung Hyo
authors: SH
authors: Jung
authors: Department of Physiology, School of Medicine, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, South Korea.
authors: Donghyen
authors: D
authors: Lee
authors: Department of Physiology, School of Medicine, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, South Korea.
authors: Dong-Youb
authors: DY
authors: Lee
authors: Department of Physiology, School of Medicine, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, South Korea.
authors: Gyoung Beom
authors: GB
authors: Lee
authors: Department of Physiology, School of Medicine, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, South Korea.
authors: Suji
authors: S
authors: Baek
authors: Department of Cosmetic Science, College of Natural Science, Hoseo University, Asan 336-795, South Korea.
authors: Do-Yoon
authors: DY
authors: Kim
authors: Department of Cosmetic Science, College of Natural Science, Hoseo University, Asan 336-795, South Korea.
authors: Hwan Myung
authors: HM
authors: Lee
authors: Department of Physiology, School of Medicine, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, South Korea.
authors: Bokyung
authors: B
authors: Kim
authors: Department of Physiology, Catholic Kwandong University College of Medicine, Kangneung 201-701, South Korea. Electronic address: skwon2028@cku.ac.kr.
authors: Seong-Chun
authors: SC
authors: Kwon
authors: Department of Physiology, School of Medicine, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, South Korea. Electronic address: kjwon@kku.ac.kr.
authors: Kyung Jong
authors: KJ
authors: Won
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000077214:Becaplermin; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D000081007:Cymenes; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D039821:Monoterpenes / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D000074624:NADPH Oxidase 1; D058426:Neointima; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010766:Phosphorylation; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000975:Antioxidants; D000081007:Cymenes; D039821:Monoterpenes; D018809:Proliferating Cell Nuclear Antigen; D020574:Proto-Oncogene Proteins c-sis; D017382:Reactive Oxygen Species; D000077214:Becaplermin; C073316:carvacrol; D006861:Hydrogen Peroxide; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Carvacrol; Migration; Neointima; Proliferation; Reactive oxygen species; Vascular smooth muscle cells