Calorie restriction protects against experimental abdominal aortic aneurysms in mice

• Published in: The Journal of experimental medicine Vol. 213; no. 11; pp. 2473 - 2488
• Main Authors: Liu, Yue, Wang, Ting-Ting, Zhang, Ran, Fu, Wen-Yan, Wang, Xu, Wang, Fang, Gao, Peng, Ding, Yang-Nan, Xie, Yan, Hao, De-Long, Chen, Hou-Zao, Liu, De-Pei
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 17.10.2016
• Subjects: 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
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.20151794

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.