- •Carvacrol inhibited PDGF-BB-stimulated RASMC migration and proliferation.
- •Carvacrol attenuated PDGF-BB-induced NOX1 expression and phosphorylation of p38 MAPK and ERK1/2 in RASMCs.
- •PDGF-BB-stimulated ROS generation was suppressed by carvacrol in RASMCs.
- •Treatment with carvacrol inhibited PDGF-BB-induced vascular sprout outgrowth.
- •Balloon injury-evoked neointima formation was reduced by carvacrol administration.
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 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.
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.
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Published online: March 28, 2015
Accepted: March 21, 2015
Received in revised form: March 1, 2015
Received: November 10, 2014
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