| Title | Intermedin(1-53) Attenuates Abdominal Aortic Aneurysm by Inhibiting Oxidative Stress |
| Authors | Lu, Wei-Wei Jia, Li-Xin Ni, Xian-Qiang Zhao, Lei Chang, Jin-Rui Zhang, Jin-Sheng Hou, Yue-Long Zhu, Yi Guan, You-Fei Yu, Yan-Rong Du, Jie Tang, Chao-Shu Qi, Yong-Fen |
| Affiliation | Capital Med Univ, Key Lab Remodeling Related Cardiovasc Dis, Beijing Inst Heart Lung & Blood Vessel Dis, Beijing An Zhen Hosp,Minist Educ, Beijing, Peoples R China. Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Key Lab Mol Cardiovasc Sci,Minist Educ, Beijing, Peoples R China. Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Pathogen Biol, Beijing, Peoples R China. 38 Xueyuan Rd, Beijing, Peoples R China. |
| Keywords | abdominal aortic aneurysm angiotensin II NAD(P)H oxidase oxidative stress E-DEFICIENT MICE SMOOTH-MUSCLE-CELL ANGIOTENSIN-II CARDIOVASCULAR HEALTH MOUSE MODELS ATHEROSCLEROSIS MECHANISMS KINASE PATHOGENESIS RECEPTOR |
| Issue Date | 2016 |
| Publisher | ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY |
| Citation | ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY.2016,36(11),2176-2190. |
| Abstract | Objective-Oxidative stress plays a critical role in the development of abdominal aortic aneurysm (AAA). Intermedin (IMD) is a regulator of oxidative stress. Here, we investigated whether IMD reduces AAA by inhibiting oxidative stress. Approach and Results-In angiotensin II-induced ApoE(-/-) mouse and CaCl2-induced C57BL/6J mouse model of AAA, IMD 1-53 significantly reduced the incidence of AAA and maximal aortic diameter. Ultrasonography, hematoxylin, and eosin staining and Verhoeff-van Gieson staining showed that IMD1-53 significantly decreased the enlarged aortas and elastic lamina degradation induced by angiotensin II or CaCl2. Mechanistically, IMD1-53 attenuated oxidative stress, inflammation, vascular smooth muscle cell apoptosis, and matrix metalloproteinase activation. IMD1-53 inhibited the activation of redox-sensitive signaling pathways, decreased the mRNA and protein expression of nicotinamide adenine dinucleotide phosphate oxidase subunits, and reduced the activity of nicotinamide adenine dinucleotide phosphate oxidase in AAA mice. Expression of Nox4 was upregulated in human AAA segments and in angiotensin II-treated mouse aortas and was markedly decreased by IMD1-53. In vitro, vascular smooth muscle cells with small-interfering RNA knockdown of IMD showed significantly increased angiotensin II-induced reactive oxygen species, and small-interfering RNA knockdown of Nox4 markedly inhibited the reactive oxygen species. IMD knockdown further increased the apoptosis of vascular smooth muscle cells and inflammation, which was reversed by Nox4 knockdown. Preincubation with IMD17-47 and protein kinase A inhibitor H89 inhibited the effect of IMD1-53, reducing Nox4 protein levels. Conclusions-IMD1-53 could have a protective effect on AAA by inhibiting oxidative stress. |
| URI | http://hdl.handle.net/20.500.11897/492874 |
| ISSN | 1079-5642 |
| DOI | 10.1161/ATVBAHA.116.307825 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 基础医学院 |
