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Calorie restriction protects against experimental abdominal aortic aneurysms in mice.


ABSTRACT: 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.

SUBMITTER: Liu Y 

PROVIDER: S-EPMC5068228 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Calorie restriction protects against experimental abdominal aortic aneurysms in mice.

Liu Yue Y   Wang Ting-Ting TT   Zhang Ran R   Fu Wen-Yan WY   Wang Xu X   Wang Fang F   Gao Peng P   Ding Yang-Nan YN   Xie Yan Y   Hao De-Long DL   Chen Hou-Zao HZ   Liu De-Pei DP  

The Journal of experimental medicine 20160926 11


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<sup>-/-</sup> mic  ...[more]

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