Catalase overexpression in aortic smooth muscle prevents pathological mechanical changes underlying abdominal aortic aneurysm formation

Am J Physiol Heart Circ Physiol. 2011 Aug;301(2):H355-62. doi: 10.1152/ajpheart.00040.2011. Epub 2011 May 6.

Abstract

The causality of the associations between cellular and mechanical mechanisms of abdominal aortic aneurysm (AAA) formation has not been completely defined. Because reactive oxygen species are established mediators of AAA growth and remodeling, our objective was to investigate oxidative stress-induced alterations in aortic biomechanics and microstructure during subclinical AAA development. We investigated the mechanisms of AAA in an angiotensin II (ANG II) infusion model of AAA in apolipoprotein E-deficient (apoE(-/-)) mice that overexpress catalase in vascular smooth muscle cells (apoE(-/-)xTg(SMC-Cat)). At baseline, aortas from apoE(-/-)xTg(SMC-Cat) exhibited increased stiffness and the microstructure was characterized by 50% more collagen content and less elastin fragmentation. ANG II treatment for 7 days in apoE(-/-) mice altered the transmural distribution of suprarenal aortic circumferential strain (quantified by opening angle, which increased from 130 ± 1° at baseline to 198 ± 8° after 7 days of ANG II treatment) without obvious changes in the aortic microstructure. No differences in aortic mechanical behavior or suprarenal opening angle were observed in apoE(-/-)xTg(SMC-Cat) after 7 days of ANG II treatment. These data suggest that at the earliest stages of AAA development H(2)O(2) is functionally important and is involved in the control of local variations in remodeling across the vessel wall. They further suggest that reduced elastin integrity at baseline may predispose the abdominal aorta to aneurysmal mechanical remodeling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Webcast

MeSH terms

  • Analysis of Variance
  • Angiotensin II
  • Animals
  • Aorta, Abdominal / enzymology*
  • Aorta, Abdominal / pathology
  • Aorta, Abdominal / physiopathology
  • Aortic Aneurysm, Abdominal / chemically induced
  • Aortic Aneurysm, Abdominal / enzymology*
  • Aortic Aneurysm, Abdominal / genetics
  • Aortic Aneurysm, Abdominal / pathology
  • Aortic Aneurysm, Abdominal / physiopathology
  • Aortic Aneurysm, Abdominal / prevention & control*
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics
  • Biomechanical Phenomena
  • Blood Pressure*
  • Catalase / genetics
  • Catalase / metabolism*
  • Collagen / metabolism
  • Disease Models, Animal
  • Elastin / metabolism
  • Hydrogen Peroxide / metabolism*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Stress, Mechanical
  • Time Factors
  • Up-Regulation

Substances

  • Apolipoproteins E
  • Angiotensin II
  • Collagen
  • Elastin
  • Hydrogen Peroxide
  • Catalase