title: Valsartan ameliorates ageing-induced aorta degeneration via angiotensin II type 1 receptor-mediated ERK activity.
abstract: Angiotensin II (Ang II) plays important roles in ageing-related disorders through its type 1 receptor (AT1 R). However, the role and underlying mechanisms of AT1R in ageing-related vascular degeneration are not well understood. In this study, 40 ageing rats were randomly divided into two groups: ageing group which received no treatment (ageing control), and valsartan group which took valsartan (selective AT1R blocker) daily for 6 months. 20 young rats were used as adult control. The aorta structure were analysed by histological staining and electron microscopy. Bcl-2/Bax expression in aorta was analysed by immunohistochemical staining, RT-PCR and Western blotting. The expressions of AT1 R, AT2 R and mitogen-activated protein kinases (MAPKs) were detected. Significant structural degeneration of aorta in the ageing rats was observed, and the degeneration was remarkably ameliorated by long-term administration of valsartan. With ageing, the expression of AT1R was elevated, the ratio of Bcl-2/Bax was decreased and meanwhile, an important subgroup of MAPKs, extracellular signal-regulated kinase (ERK) activity was elevated. However, these changes in ageing rats could be reversed to some extent by valsartan. In vitro experiments observed consistent results as in vivo study. Furthermore, ERK inhibitor could also acquire partial effects as valsartan without affecting AT1R expression. The results indicated that AT1R involved in the ageing-related degeneration of aorta and AT1R-mediated ERK activity was an important mechanism underlying the process.
authors.affiliation: Department of Gerontology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.
authors.forename: HaiYan
authors.initials: H
authors.lastname: Shan
authors.forename: Siyang
authors.initials: S
authors.lastname: Zhang
authors.forename: Xuelian
authors.initials: X
authors.lastname: Li
authors.forename: Kai
authors.initials: K
authors.lastname: Yu
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Xinyue
authors.initials: X
authors.lastname: Chen
authors.forename: Bo
authors.initials: B
authors.lastname: Jin
authors.forename: XiaoJuan
authors.initials: X
authors.lastname: Bai
mesh_terms: D000375:Aging; D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D015153:Blotting, Western; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D044140:Receptor, Angiotensin, Type 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013777:Tetrazoles / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D000804:Angiotensin II; D000068756:Valsartan; D048049:Extracellular Signal-Regulated MAP Kinases; D014633:Valine
keywords: Bax; Bcl-2; angiotensin II; mitogen-activated protein kinase; valsartan; vascular ageing