title: Age-Associated Changes in the Vascular Renin-Angiotensin System in Mice.
abstract: Background. This study evaluated whether the change in the renin-angiotensin system (RAS) is associated with arterial aging in mice. Methods. Histologic changes and expressions of transforming growth factor-β (TGF-β), collagen IV, fibronectin, angiotensin II (Ang II), angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), angiotensin II type 1 receptor (AT1R), angiotensin II type 2 receptor (AT2R), prorenin receptor (PRR), Mas receptor (MasR), endothelial nitric oxide synthase (eNOS), NADPH oxidase 2 and oxidase 4 (Nox2 and Nox4), 8-hydroxy-2'-deoxyguanosine (8-OHdG), 3-nitrotyrosine, and superoxide dismutase 1 and dismutase 2 (SOD1 and SOD2) were measured in the thoracic aortas from 2-month-old, 12-month-old, and 24-month-old C57/BL6 mice. Results. Twenty-four-month-old mice showed significantly increased aortic media thickness and expressions of TGF-β, collagen IV, and fibronectin, compared to 2-month-old and 12-month-old mice. The expressions of PRR, ACE, and Ang II, and AT1R-positive area significantly increased, whereas expressions of ACE2 and MasR and AT2R-positive area decreased with age. The expressions of phosphorylated serine(1177)-eNOS, SOD1, and SOD2 decreased, and the 8-OHdG-positive area and the 3-nitrotyrosine-positive area increased with age. The expression of Nox2 significantly increased with age, but that of Nox4 did not change. Conclusions. The enhanced PRR-ACE-Ang II-AT1R axis and reduced ACE2-MasR axis were associated with arterial aging in mice.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 137701, Republic of Korea; Department of Internal Medicine, Incheon St. Mary's Hospital, Incheon, Republic of Korea.
authors.forename: Hye Eun
authors.initials: HE
authors.lastname: Yoon
authors.affiliation: Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 137701, Republic of Korea.
authors.forename: Eun Nim
authors.initials: EN
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 137701, Republic of Korea.
authors.forename: Min Young
authors.initials: MY
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 137701, Republic of Korea.
authors.forename: Ji Hee
authors.initials: JH
authors.lastname: Lim
authors.affiliation: Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 137701, Republic of Korea; Department of Internal Medicine, Seoul St. Mary's Hospital, Seoul, Republic of Korea.
authors.forename: In-Ae
authors.initials: IA
authors.lastname: Jang
authors.affiliation: Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 137701, Republic of Korea; Department of Internal Medicine, Seoul St. Mary's Hospital, Seoul, Republic of Korea.
authors.forename: Tae Hyun
authors.initials: TH
authors.lastname: Ban
authors.affiliation: Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 137701, Republic of Korea; Department of Internal Medicine, Incheon St. Mary's Hospital, Incheon, Republic of Korea.
authors.forename: Seok Joon
authors.initials: SJ
authors.lastname: Shin
authors.affiliation: Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 137701, Republic of Korea; Department of Internal Medicine, Seoul St. Mary's Hospital, Seoul, Republic of Korea.
authors.forename: Cheol Whee
authors.initials: CW
authors.lastname: Park
authors.affiliation: Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 137701, Republic of Korea; Department of Internal Medicine, Yeouido St. Mary's Hospital, Seoul, Republic of Korea.
authors.forename: Yoon Sik
authors.initials: YS
authors.lastname: Chang
authors.affiliation: Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 137701, Republic of Korea; Department of Internal Medicine, Seoul St. Mary's Hospital, Seoul, Republic of Korea.
authors.forename: Bum Soon
authors.initials: BS
authors.lastname: Choi
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000375:Aging / Q000378:metabolism*; D000804:Angiotensin II / Q000097:blood; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism*; D015153:Blotting, Western; D024141:Collagen Type IV / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005353:Fibronectins / Q000378:metabolism; D007150:Immunohistochemistry; D008810:Mice, Inbred C57BL; D019255:NADPH Oxidases / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System; D013482:Superoxide Dismutase / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D024141:Collagen Type IV; D005353:Fibronectins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D044139:Receptor, Angiotensin, Type 2; D043562:Receptors, G-Protein-Coupled; D016212:Transforming Growth Factor beta; D000804:Angiotensin II; C002744:3-nitrotyrosine; D014443:Tyrosine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D007703:Peptidyl-Dipeptidase A; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2; D012083:Renin; D003849:Deoxyguanosine