Intermedin1-53 Attenuates Abdominal Aortic Aneurysm by Inhibiting Oxidative Stress.

Autor:	Lu WW; From the Key Laboratory of Remodeling-Related Cardiovascular Diseases, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing An Zhen Hospital, Capital Medical University, Ministry of Education, China (W.-W.L., L.-X.J., X.-Q.N., L.Z., Y.-L.H., J.D., Y.-F.Q.); Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China (W.-W.L., X.-Q.N., L.Z., J.-R.C., J.-S.Z., Y.Z., Y.-F.G., C.-S.T., Y.-F.Q.); and Department of Pathogen Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China (W.-W.L., X.-Q.N., J.-S.Z., Y.-L.H., Y.-R.Y., Y.-F.Q.)., Jia LX; From the Key Laboratory of Remodeling-Related Cardiovascular Diseases, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing An Zhen Hospital, Capital Medical University, Ministry of Education, China (W.-W.L., L.-X.J., X.-Q.N., L.Z., Y.-L.H., J.D., Y.-F.Q.); Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China (W.-W.L., X.-Q.N., L.Z., J.-R.C., J.-S.Z., Y.Z., Y.-F.G., C.-S.T., Y.-F.Q.); and Department of Pathogen Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China (W.-W.L., X.-Q.N., J.-S.Z., Y.-L.H., Y.-R.Y., Y.-F.Q.)., Ni XQ; From the Key Laboratory of Remodeling-Related Cardiovascular Diseases, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing An Zhen Hospital, Capital Medical University, Ministry of Education, China (W.-W.L., L.-X.J., X.-Q.N., L.Z., Y.-L.H., J.D., Y.-F.Q.); Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China (W.-W.L., X.-Q.N., L.Z., J.-R.C., J.-S.Z., Y.Z., Y.-F.G., C.-S.T., Y.-F.Q.); and Department of Pathogen Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China (W.-W.L., X.-Q.N., J.-S.Z., Y.-L.H., Y.-R.Y., Y.-F.Q.)., Zhao L; From the Key Laboratory of Remodeling-Related Cardiovascular Diseases, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing An Zhen Hospital, Capital Medical University, Ministry of Education, China (W.-W.L., L.-X.J., X.-Q.N., L.Z., Y.-L.H., J.D., Y.-F.Q.); Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China (W.-W.L., X.-Q.N., L.Z., J.-R.C., J.-S.Z., Y.Z., Y.-F.G., C.-S.T., Y.-F.Q.); and Department of Pathogen Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China (W.-W.L., X.-Q.N., J.-S.Z., Y.-L.H., Y.-R.Y., Y.-F.Q.)., Chang JR; From the Key Laboratory of Remodeling-Related Cardiovascular Diseases, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing An Zhen Hospital, Capital Medical University, Ministry of Education, China (W.-W.L., L.-X.J., X.-Q.N., L.Z., Y.-L.H., J.D., Y.-F.Q.); Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China (W.-W.L., X.-Q.N., L.Z., J.-R.C., J.-S.Z., Y.Z., Y.-F.G., C.-S.T., Y.-F.Q.); and Department of Pathogen Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China (W.-W.L., X.-Q.N., J.-S.Z., Y.-L.H., Y.-R.Y., Y.-F.Q.)., Zhang JS; From the Key Laboratory of Remodeling-Related Cardiovascular Diseases, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing An Zhen Hospital, Capital Medical University, Ministry of Education, China (W.-W.L., L.-X.J., X.-Q.N., L.Z., Y.-L.H., J.D., Y.-F.Q.); Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China (W.-W.L., X.-Q.N., L.Z., J.-R.C., J.-S.Z., Y.Z., Y.-F.G., C.-S.T., Y.-F.Q.); and Department of Pathogen Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China (W.-W.L., X.-Q.N., J.-S.Z., Y.-L.H., Y.-R.Y., Y.-F.Q.)., Hou YL; From the Key Laboratory of Remodeling-Related Cardiovascular Diseases, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing An Zhen Hospital, Capital Medical University, Ministry of Education, China (W.-W.L., L.-X.J., X.-Q.N., L.Z., Y.-L.H., J.D., Y.-F.Q.); Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China (W.-W.L., X.-Q.N., L.Z., J.-R.C., J.-S.Z., Y.Z., Y.-F.G., C.-S.T., Y.-F.Q.); and Department of Pathogen Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China (W.-W.L., X.-Q.N., J.-S.Z., Y.-L.H., Y.-R.Y., Y.-F.Q.)., Zhu Y; From the Key Laboratory of Remodeling-Related Cardiovascular Diseases, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing An Zhen Hospital, Capital Medical University, Ministry of Education, China (W.-W.L., L.-X.J., X.-Q.N., L.Z., Y.-L.H., J.D., Y.-F.Q.); Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China (W.-W.L., X.-Q.N., L.Z., J.-R.C., J.-S.Z., Y.Z., Y.-F.G., C.-S.T., Y.-F.Q.); and Department of Pathogen Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China (W.-W.L., X.-Q.N., J.-S.Z., Y.-L.H., Y.-R.Y., Y.-F.Q.)., Guan YF; From the Key Laboratory of Remodeling-Related Cardiovascular Diseases, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing An Zhen Hospital, Capital Medical University, Ministry of Education, China (W.-W.L., L.-X.J., X.-Q.N., L.Z., Y.-L.H., J.D., Y.-F.Q.); Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China (W.-W.L., X.-Q.N., L.Z., J.-R.C., J.-S.Z., Y.Z., Y.-F.G., C.-S.T., Y.-F.Q.); and Department of Pathogen Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China (W.-W.L., X.-Q.N., J.-S.Z., Y.-L.H., Y.-R.Y., Y.-F.Q.)., Yu YR; From the Key Laboratory of Remodeling-Related Cardiovascular Diseases, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing An Zhen Hospital, Capital Medical University, Ministry of Education, China (W.-W.L., L.-X.J., X.-Q.N., L.Z., Y.-L.H., J.D., Y.-F.Q.); Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China (W.-W.L., X.-Q.N., L.Z., J.-R.C., J.-S.Z., Y.Z., Y.-F.G., C.-S.T., Y.-F.Q.); and Department of Pathogen Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China (W.-W.L., X.-Q.N., J.-S.Z., Y.-L.H., Y.-R.Y., Y.-F.Q.)., Du J; From the Key Laboratory of Remodeling-Related Cardiovascular Diseases, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing An Zhen Hospital, Capital Medical University, Ministry of Education, China (W.-W.L., L.-X.J., X.-Q.N., L.Z., Y.-L.H., J.D., Y.-F.Q.); Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China (W.-W.L., X.-Q.N., L.Z., J.-R.C., J.-S.Z., Y.Z., Y.-F.G., C.-S.T., Y.-F.Q.); and Department of Pathogen Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China (W.-W.L., X.-Q.N., J.-S.Z., Y.-L.H., Y.-R.Y., Y.-F.Q.)., Tang CS; From the Key Laboratory of Remodeling-Related Cardiovascular Diseases, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing An Zhen Hospital, Capital Medical University, Ministry of Education, China (W.-W.L., L.-X.J., X.-Q.N., L.Z., Y.-L.H., J.D., Y.-F.Q.); Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China (W.-W.L., X.-Q.N., L.Z., J.-R.C., J.-S.Z., Y.Z., Y.-F.G., C.-S.T., Y.-F.Q.); and Department of Pathogen Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China (W.-W.L., X.-Q.N., J.-S.Z., Y.-L.H., Y.-R.Y., Y.-F.Q.)., Qi YF; From the Key Laboratory of Remodeling-Related Cardiovascular Diseases, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing An Zhen Hospital, Capital Medical University, Ministry of Education, China (W.-W.L., L.-X.J., X.-Q.N., L.Z., Y.-L.H., J.D., Y.-F.Q.); Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China (W.-W.L., X.-Q.N., L.Z., J.-R.C., J.-S.Z., Y.Z., Y.-F.G., C.-S.T., Y.-F.Q.); and Department of Pathogen Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China (W.-W.L., X.-Q.N., J.-S.Z., Y.-L.H., Y.-R.Y., Y.-F.Q.). yongfenqi@163.com.
Jazyk:	angličtina
Zdroj:	Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2016 Nov; Vol. 36 (11), pp. 2176-2190. Date of Electronic Publication: 2016 Sep 15.
DOI:	10.1161/ATVBAHA.116.307825
Abstrakt:	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 CaCl 2 -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 IMD 1- 53 significantly decreased the enlarged aortas and elastic lamina degradation induced by angiotensin II or CaCl 2 . Mechanistically, IMD 1- 53 attenuated oxidative stress, inflammation, vascular smooth muscle cell apoptosis, and matrix metalloproteinase activation. IMD 1- 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 IMD 1- 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 IMD 17- 47 and protein kinase A inhibitor H89 inhibited the effect of IMD 1-53 , reducing Nox4 protein levels. Conclusions: IMD 1- 53 could have a protective effect on AAA by inhibiting oxidative stress. (© 2016 American Heart Association, Inc.)
Databáze:	MEDLINE
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