title: Naringenin inhibits angiotensin II-induced vascular smooth muscle cells proliferation and migration and decreases neointimal hyperplasia in balloon injured rat carotid arteries through suppressing oxidative stress.
abstract: Proliferation and migration of vascular smooth muscle cells (VSMCs) play pivotal roles in the development of restenosis after angioplasty and oxidative stress involves both processes. Naringenin, a flavanone compound found in citrus fruits, has been widely evaluated for antioxidant activity. This study was designed to explore whether naringenin could inhibit angiotensin II-induced VSMCs proliferation and migration and decrease neointimal hyperplasia in balloon injured rat carotid arteries. VSMCs were treated with or without naringenin before stimulation with 1 µM angiotensin II and twenty-four rats were subjected to carotid arteries injury and the carotid arteries were harvested at 14 d after balloon injury. The results showed naringenin led to a significant inhibition of angiotensin II-induced VSMCs proliferation and migration. Naringenin significantly attenuated the reactive oxygen species production, increased the superoxide dismutase activity and decreased the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, reduced phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) and the nuclear translocation of nuclear factor (NF)-κB p65 in angiotensin II-treated VSMCs. Moreover, naringenin decreased the ratio of neointima to media by 63.8% in balloon injured rat carotid arteries, and the serum level of 8-iso-prostaglandin F2α in naringenin-treated rats was significantly decreased. These results indicated naringenin exhibited antioxidant activity on angiotensin II-treated VSMCs and balloon injured rat carotid arteries and could be a potential protective agent for restenosis after angioplasty.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University; Cardiovascular Research Institute of Wuhan University.
authors.forename: Changwu
authors.initials: C
authors.lastname: Xu
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Hu
authors.forename: Xiaoya
authors.initials: X
authors.lastname: Zhou
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Lu
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D002339:Carotid Arteries / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020212:Carotid Artery Injuries / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002957:Citrus / Q000737:chemistry*; D023903:Coronary Restenosis / Q000378:metabolism / Q000517:prevention & control; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology* / Q000627:therapeutic use; D006965:Hyperplasia; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology
chemical_list: D000975:Antioxidants; D044950:Flavanones; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D051996:Transcription Factor RelA; D000804:Angiotensin II; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; C005273:naringenin