title: Valsartan attenuates intimal hyperplasia in balloon-injured rat aortic arteries through modulating the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas receptor axis.
abstract: The role of the Mas receptor in the activity of valsartan against intimal hyperplasia is unclear. Herein, we investigated the role of the angiotensin-converting enzyme 2 (ACE2)-angiotensin-(1-7)-Mas receptor axis on the activity of valsartan against intimal hyperplasiain balloon-injured rat aortic arteries. Wistar rats were randomized equally into the sham control group, injured group, and injured plus valsartan (20 mg/kg/d)-treated group. Valsartan significantly attenuated the vascular smooth muscle cell proliferation and intimal and medial thickening on days 14 and 28 after injury. The angiotensin-(1-7) levels as well as ACE2 and Mas receptor mRNA/protein expression were significantly decreased in the injured rats, compared to the uninjured rats; meanwhile, the angiotensin II level as well as the ACE and AT1 receptor mRNA/protein expression were increased (all P < 0.05 or < 0.01). Additionally, the p-ERK protein expression was increased (P < 0.01). Treatment with valsartan significantly increased the angiotensin-(1-7) levels as well as ACE2 and Mas receptor mRNA/protein expression but decreased the angiotensin II level, ACE and AT1 receptor mRNA/protein expression, as well as the p-ERK protein expression, compared to the injured group (all P < 0.05 or < 0.01). These results suggest that valsartan attenuates neointimal hyperplasiain balloon-injured rat aortic arteries through activation of the ACE2-angiotensin-(1-7)-Mas axis as well as inhibition of the ACE-angiotensin II-AT1 and p-ERK pathways.
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266003, China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266003, China.
authors.forename: Shanglang
authors.initials: S
authors.lastname: Cai
authors.affiliation: Hypertension Laboratory, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Qixin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Emergency, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266003, China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266003, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Hou
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266003, China.
authors.forename: Haichu
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Cardiology, Qilu Hospital of Shandong University, Shandong University, Jinan 250012, China. Electronic address: liyonghong-66@163.com.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Ge
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266003, China.
authors.forename: Renyan
authors.initials: R
authors.lastname: Guan
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266003, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001011:Aorta / Q000201:enzymology / Q000293:injuries / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006965:Hyperplasia; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis*; D017539:Tunica Intima / Q000201:enzymology / Q000293:injuries / Q000473:pathology; D000068756:Valsartan / Q000494:pharmacology*
chemical_list: D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D044140:Receptor, Angiotensin, Type 1; D043562:Receptors, G-Protein-Coupled; D000068756:Valsartan; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2
keywords: Angiotensin-converting enzyme 2; Balloon injury; Extracellular signal-regulated kinase; Mas receptor; Valsartan