title: Nobiletin Inhibits PDGF-BB-induced vascular smooth muscle cell proliferation and migration and attenuates neointimal hyperplasia in a rat carotid artery injury model.
abstract: Preclinical Research The abnormal migration and proliferation of vascular smooth muscle cells (VSMCs) plays a pivotal role in the development of neointimal hyperplasia after vascular injury. Nobiletin, a citrus bioflavonoid, exhibits anti-inflammatory and anti-oxidative activities. The present study evalutaed whether nobiletin could inhibit platelet-derived growth factor (PDGF)-BB- stimulated VSMC proliferation and migration and decrease neointimal hyperplasia in a rat carotid artery injury model. Cultured VSMCs from rat thoracic aortas were treated with nobiletin before being stimulated with 20 ng/ml PDGF-BB, and rats were subjected to carotid artery injury. Nobiletin inhibited PDGF-BB-induced VSMC proliferation and migration, attenuated reactive oxygen species (ROS) production and reduced phosphorylation of ERK1/2 and the expression of nuclear NF-κB p65 in PDGF-BB-stimulated VSMCs. Nobiletin decreased the intima area and the ratio of neointima to media in balloon-injured rat carotid arteries. Serum levels of TNF-α and IL-6 in nobiletin-treated rats were decreased. These results indicated that nobiletin could be a potential protective agent for the prevention and treatment of restenosis after angioplasty.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China; Department of Cardiology, Xiangyang Central Hospital, Hospital Affiliated to Hubei University of Arts and Science, Xiangyang, 441021, China.
authors.forename: Siyu
authors.initials: S
authors.lastname: Guan
authors.forename: Qizhu
authors.initials: Q
authors.lastname: Tang
authors.forename: Wenwei
authors.initials: W
authors.lastname: Liu
authors.forename: Rui
authors.initials: R
authors.lastname: Zhu
authors.forename: Bin
authors.initials: B
authors.lastname: Li
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000293:injuries* / Q000378:metabolism; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D047309:Flavones / Q000008:administration & dosage* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D058426:Neointima / Q000378:metabolism / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D047309:Flavones; D017382:Reactive Oxygen Species; C008661:nobiletin
keywords: artery injury; neointimal hyperplasia; nobiletin; vascular smooth muscle cells