Scientific article

NOX1 deficiency protects from aortic dissection in response to angiotensin II

Published inHypertension, vol. 50, no. 1, p. 189-196
Publication date2007

Oxidative stress leads to vascular damage and participates in the pathomechanisms of aortic dissection and aneurysm formation. Here we study aortic dissection in mice deficient in the superoxide-generating reduced nicotinamide-adenine dinucleotide phosphate oxidase NOX1. Seven days of treatment with the hypertensive agent angiotensin II (3 mg/kg per day) led to aortic dissection in 23% of wild-type C57BL/6J mice but in only 4% of NOX1-deficient mice (P=0.05). In contrast, treatment of wild-type C57BL/6J mice with the hypertensive agent norepinephrine (12 mg/kg per day), did not lead to aortic dissection or sudden death, suggesting that hypertension is not sufficient to cause aortic dissection. Interestingly, norepinephrine-dependent blood pressure elevations were conserved in NOX1-deficient mice, demonstrating that, different from angiotensin II, it acts through NOX1-independent hypertensive mechanisms. The resistance of NOX1-deficient mice to angiotensin II-induced aortic dissection suggests a role for NOX1-dependent alterations of the vascular wall. We, therefore, studied gene expression and protease/inhibitor equilibrium. cDNA array analysis demonstrated differential effects of angiotensin II on gene expression in wild-type and NOX1-deficient mice. Tissue inhibitor of metalloproteinase 1 was increased both on the mRNA and the protein level in aortas from NOX1-deficient mice. Thus, our results demonstrate that NOX1 is involved in the mechanisms of angiotensin II-dependent aortic dissection. As one underlying mechanism, we have identified NOX1-dependent suppression of tissue inhibitor of metalloproteinase 1 expression, which could lead to tissue damage through an altered protease/inhibitor balance.

  • Aneurysm, Dissecting/ chemically induced/ prevention & control
  • Angiotensin II
  • Animals
  • Aorta, Thoracic/metabolism
  • Aortic Aneurysm/ chemically induced/ prevention & control
  • Blood Pressure/drug effects
  • Disease Susceptibility
  • Gene Expression Regulation/drug effects
  • Hypertension/chemically induced
  • Male
  • Matrix Metalloproteinase 2/metabolism
  • Matrix Metalloproteinase 9/metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NADPH Oxidase/ deficiency
  • Norepinephrine/pharmacology
  • RNA, Messenger/metabolism
  • Tissue Inhibitor of Metalloproteinase-1/genetics/metabolism
  • Vasoconstrictor Agents
Citation (ISO format)
GAVAZZI, Gaetan et al. NOX1 deficiency protects from aortic dissection in response to angiotensin II. In: Hypertension, 2007, vol. 50, n° 1, p. 189–196. doi: 10.1161/HYPERTENSIONAHA.107.089706
Updates (1)
ISSN of the journal0194-911X

Technical informations

Creation08/27/2010 1:34:36 PM
First validation08/27/2010 1:34:36 PM
Update time03/14/2023 4:03:23 PM
Status update03/14/2023 4:03:23 PM
Last indexation08/28/2023 7:34:03 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack