Calorie restriction protects against experimental abdominal aortic aneurysms in mice
| Autor: | Xu Wang, De-Long Hao, Yang-Nan Ding, Yue Liu, Yan Xie, Fang Wang, Peng Gao, Ran Zhang, Tingting Wang, Hou-Zao Chen, Wenyan Fu, De-Pei Liu |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Male Vascular smooth muscle environment and public health Muscle Smooth Vascular Oxidative Phosphorylation Epigenesis Genetic Histones Mice Sirtuin 1 Immunology and Allergy Promoter Regions Genetic Aorta Research Articles Mice Knockout Angiotensin II Abdominal aorta Acetylation Lipids Abdominal aortic aneurysm Chromatin Liver cardiovascular system Matrix Metalloproteinase 2 medicine.medical_specialty Immunology Calorie restriction Myocytes Smooth Muscle macromolecular substances Biology Article 03 medical and health sciences Histone H3 Aneurysm Apolipoproteins E Internal medicine medicine.artery medicine Animals Caloric Restriction Lysine medicine.disease Lipid Metabolism Surgery Mice Inbred C57BL enzymes and coenzymes (carbohydrates) 030104 developmental biology Endocrinology Glucose biology.protein Aortic Aneurysm Abdominal |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 |
| Popis: | Liu and collaborators show that calorie restriction limits the severity of abdominal aortic aneurysms in mice by modulating the activity of the energy sensor SIRT1 in vascular smooth muscle cells. 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. |
| Databáze: | OpenAIRE |
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