Calorie restriction protects against experimental abdominal aortic aneurysms in mice.
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.
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Yue
Y
Liu
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Ting-Ting
TT
Wang
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Ran
R
Zhang
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Wen-Yan
0000-0001-8895-2038
WY
Fu
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Xu
X
Wang
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Fang
F
Wang
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Peng
P
Gao
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Yang-Nan
0000-0002-3907-6147
YN
Ding
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Yan
Y
Xie
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
De-Long
DL
Hao
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China liudp@pumc.edu.cn chenhouzao@ibms.cams.cn.
Hou-Zao
HZ
Chen
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China liudp@pumc.edu.cn chenhouzao@ibms.cams.cn.
De-Pei
DP
Liu
D000107:Acetylation; D000804:Angiotensin II; D000818:Animals; D001011:Aorta / Q000378:metabolism; D017544:Aortic Aneurysm, Abdominal / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency / Q000378:metabolism; D031204:Caloric Restriction; D002843:Chromatin / Q000378:metabolism; D044127:Epigenesis, Genetic; D005947:Glucose / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D010085:Oxidative Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D056564:Sirtuin 1 / Q000378:metabolism
D001057:Apolipoproteins E; D002843:Chromatin; D006657:Histones; D008055:Lipids; D000804:Angiotensin II; D020778:Matrix Metalloproteinase 2; D056564:Sirtuin 1; D005947:Glucose; D008239:Lysine
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