title: Overexpression of angiotensin II type 2 receptor suppresses neointimal hyperplasia in a rat carotid arterial balloon injury model.
abstract: Angiotensin II (ANG II) type 2 receptor (AT2R) has been recognized to suppress the proliferation of vascular smooth muscle cells (VSMCs). The aim of the present study was to determine whether AT2R overexpression inhibits neointimal hyperplasia in a rat carotid arterial balloon injury model and to examine the underlying mechanisms of its activity. Balloon-injured rats receiving Ad-AT2R showed significant diminutions in neointimal area and intima/media ratio compared to non-treated rats or rats receiving adenovirus containing green fluorescent protein (Ad-GFP). In addition, extracellular regulated kinase 1/2 (ERK1/2) and basic transcription element-binding protein 2 (BTEB2) were significantly down-regulated in the arteries and VSMCs of Ad-AT2R-treated rats and compared to Ad-GFP-treated rats. However, Ad-AT2R transfection failed to affect the expression of ANG II type 1 receptor (AT1R) in carotid arteries and cultured VSMCs. The present study provides direct evidence that AT2R plays a beneficial role in balloon injury-induced neointimal hyperplasia, which is mainly attributed to the inhibition of VSMC proliferation and involves the down-regulation of the ERK1/2 and BTEB2 pathways, but is independent of the expression of AT1R.
authors.affiliation: Department of Cardiology, General Hospital of PLA Chengdu Military Area Command, Chengdu 610083, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Tang
authors.forename: Shuangtao
authors.initials: S
authors.lastname: Ma
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Yang
authors.forename: Dachun
authors.initials: D
authors.lastname: Yang
authors.forename: Jinsong
authors.initials: J
authors.lastname: Chen
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Su
authors.forename: Yan
authors.initials: Y
authors.lastname: Tan
authors.forename: Meiqin
authors.initials: M
authors.lastname: Sun
authors.forename: De
authors.initials: D
authors.lastname: Li
mesh_terms: D000818:Animals; D020212:Carotid Artery Injuries / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D002404:Catheterization; D002478:Cells, Cultured; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006965:Hyperplasia; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D051381:Rats; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D017539:Tunica Intima / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*
chemical_list: C492215:Klf5 protein, rat; D051741:Kruppel-Like Transcription Factors; D044139:Receptor, Angiotensin, Type 2; D048049:Extracellular Signal-Regulated MAP Kinases