Calorie restriction protects against experimental abdominal aortic aneurysms in mice

J Exp Med. 2016 Oct 17;213(11):2473-2488. doi: 10.1084/jem.20151794. Epub 2016 Sep 26.


Abdominal aortic aneurysm (AAA), characterized by a localized dilation of the abdominal aorta, is a life-threatening vascular pathology. Because of the current lack of effective treatment for AAA rupture, prevention is of prime importance for AAA management. Calorie restriction (CR) is a nonpharmacological intervention that delays the aging process and provides various health benefits. However, whether CR prevents AAA formation remains untested. In this study, we subjected Apoe-/- mice to 12 wk of CR and then examined the incidence of angiotensin II (AngII)-induced AAA formation. We found that CR markedly reduced the incidence of AAA formation and attenuated aortic elastin degradation in Apoe-/- mice. The expression and activity of Sirtuin 1 (SIRT1), a key metabolism/energy sensor, were up-regulated in vascular smooth muscle cells (VSMCs) upon CR. Importantly, the specific ablation of SIRT1 in smooth muscle cells abolished the preventive effect of CR on AAA formation in Apoe-/- mice. Mechanistically, VSMC-SIRT1-dependent deacetylation of histone H3 lysine 9 on the matrix metallopeptidase 2 (Mmp2) promoter was required for CR-mediated suppression of AngII-induced MMP2 expression. Together, our findings suggest that CR may be an effective intervention that protects against AAA formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Angiotensin II
  • Animals
  • Aorta / metabolism
  • Aortic Aneurysm, Abdominal / blood
  • Aortic Aneurysm, Abdominal / chemically induced*
  • Aortic Aneurysm, Abdominal / metabolism
  • Aortic Aneurysm, Abdominal / prevention & control*
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / metabolism
  • Caloric Restriction*
  • Chromatin / metabolism
  • Epigenesis, Genetic
  • Glucose / metabolism
  • Histones / metabolism
  • Lipid Metabolism / genetics
  • Lipids / blood
  • Liver / metabolism
  • Lysine / metabolism
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Smooth, Vascular / pathology
  • Myocytes, Smooth Muscle / metabolism
  • Oxidative Phosphorylation
  • Promoter Regions, Genetic / genetics
  • Sirtuin 1 / metabolism


  • Apolipoproteins E
  • Chromatin
  • Histones
  • Lipids
  • Angiotensin II
  • Matrix Metalloproteinase 2
  • Sirtuin 1
  • Glucose
  • Lysine