Age-Associated Changes in the Vascular Renin-Angiotensin System in Mice

Oxid Med Cell Longev. 2016:2016:6731093. doi: 10.1155/2016/6731093. Epub 2016 Apr 20.

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.

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Aging / metabolism*
  • Angiotensin II / blood
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Aorta, Thoracic / metabolism*
  • Blotting, Western
  • Collagen Type IV / metabolism
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Fibronectins / metabolism
  • Immunohistochemistry
  • Mice, Inbred C57BL
  • NADPH Oxidases / metabolism
  • Nitric Oxide Synthase Type III / metabolism
  • Oxidative Stress
  • Peptidyl-Dipeptidase A / metabolism
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / metabolism
  • Receptor, Angiotensin, Type 2 / metabolism
  • Receptors, G-Protein-Coupled / metabolism
  • Renin / blood
  • Renin-Angiotensin System*
  • Superoxide Dismutase / metabolism
  • Transforming Growth Factor beta / metabolism
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism

Substances

  • Collagen Type IV
  • Fibronectins
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Receptor, Angiotensin, Type 2
  • Receptors, G-Protein-Coupled
  • Transforming Growth Factor beta
  • Angiotensin II
  • 3-nitrotyrosine
  • Tyrosine
  • 8-Hydroxy-2'-Deoxyguanosine
  • Nitric Oxide Synthase Type III
  • Superoxide Dismutase
  • NADPH Oxidases
  • Peptidyl-Dipeptidase A
  • Ace2 protein, mouse
  • Angiotensin-Converting Enzyme 2
  • Renin
  • Deoxyguanosine