Absence of p55 TNF receptor reduces atherosclerosis, but has no major effect on angiotensin II induced aneurysms in LDL receptor deficient mice

PLoS One. 2009 Jul 7;4(7):e6113. doi: 10.1371/journal.pone.0006113.


Background: The aim of the current study was to investigate the role of p55 TNF Receptor (p55 TNFR), the main signaling receptor for the pro-inflammatory cytokine tumor necrosis factor (TNF), in the development of two vascular disorders: atherosclerosis and angiotensin (Ang) II-induced abdominal aortic aneurysms (AAA).

Methodology/principal findings: p55 TNFR deficient mice were crossed to an LDL receptor deficient background and were induced for the development of either atherosclerosis or AngII-induced AAA, and compared to littermate controls, wild-type for p55 TNFR expression. p55 TNFR deficient mice developed 43% smaller atherosclerotic lesions in the aortic sinuses compared to controls. Moreover, expression of CD68, a macrophage specific marker, exhibited a 50% reduction in the aortic arches. Decreased atherosclerosis correlated with a strong down-regulation in the expression of adhesion molecules, such as VCAM-1 and ICAM-1, by p55 TNFR deficient endothelium. In addition, expression levels of the pro-inflammatory cytokines and chemokines TNF, IL-6, MCP-1 and RANTES were significantly reduced in aortas of p55 TNFR deficient mice. In contrast, in the AngII-induced model of AAA, p55 TNFR deficiency correlated with a slight trend towards increased aneurismal lethality, but the incidence of aortic rupture due to a dissecting aneurysm, and the expansion of the suprarenal aorta were not significantly different compared to controls.

Conclusion/significance: We found that p55 TNFR expression promotes atherosclerosis, among other mechanisms, by enhancing expression of endothelial adhesion molecules, while it seems to have no major role in the development of AngII-induced AAA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / physiology*
  • Animals
  • Aortic Aneurysm, Abdominal / genetics
  • Aortic Aneurysm, Abdominal / physiopathology*
  • Atherosclerosis / physiopathology*
  • Chemokines / metabolism
  • Cytokines / metabolism
  • Mice
  • Mice, Knockout
  • Receptors, LDL / genetics
  • Receptors, LDL / physiology*
  • Receptors, Tumor Necrosis Factor, Type I / genetics
  • Receptors, Tumor Necrosis Factor, Type I / metabolism
  • Receptors, Tumor Necrosis Factor, Type I / physiology*
  • Signal Transduction


  • Chemokines
  • Cytokines
  • Receptors, LDL
  • Receptors, Tumor Necrosis Factor, Type I
  • Angiotensin II