Dickkopf-3 protects against cardiac dysfunction and ventricular remodelling following myocardial infarction
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- 作者：Ming-Wei Bao ; Zhongxiang Cai ; Xiao-Jing Zhang ; Liangpeng Li…
- 关键词：DKK3 ; Myocardial infarction ; Cardiac remodelling ; Apoptosis ; Inflammation ; ASK1
- 刊名：Basic Research in Cardiology
- 出版年：2015
- 出版时间：May 2015
- 年：2015
- 卷：110
- 期：3
- 全文大小：3,895 KB
- 参考文献：1. Abarzua, F, Sakaguchi, M, Takaishi, M, Nasu, Y, Kurose, K, Ebara, S, Miyazaki, M, Namba, M, Kumon, H, Huh, NH (2005) Adenovirus-mediated overexpression of REIC/Dkk-3 selectively induces apoptosis in human prostate cancer cells through activation of c-Jun-NH2-kinase. Cancer Res 65: pp. 9617-9622 CrossRef
2. Abe, J, Baines, CP, Berk, BC (2000) Role of mitogen-activated protein kinases in ischemia and reperfusion injury: the good and the bad. Circ Res 86: pp. 607-609 CrossRef
3. Barancik, M, Htun, P, Strohm, C, Kilian, S, Schaper, W (2000) Inhibition of the cardiac p38-MAPK pathway by SB203580 delays ischemic cell death. J Cardiovasc Pharmacol 35: pp. 474-483 CrossRef
4. Barrantes Idel, B, Montero-Pedrazuela, A, Guadano-Ferraz, A, Obregon, MJ, Martinez de Mena, R, Gailus-Durner, V, Fuchs, H, Franz, TJ, Kalaydjiev, S, Klempt, M, Holter, S, Rathkolb, B, Reinhard, C, Morreale de Escobar, G, Bernal, J, Busch, DH, Wurst, W, Wolf, E, Schulz, H, Shtrom, S, Greiner, E, Hrabe de Angelis, M, Westphal, H, Niehrs, C (2006) Generation and characterization of dickkopf3 mutant mice. Mol Cell Biol 26: pp. 2317-2326 CrossRef
5. Bharti, K, Gasper, M, Ou, J, Brucato, M, Clore-Gronenborn, K, Pickel, J, Arnheiter, H (2012) A regulatory loop involving PAX6, MITF, and WNT signaling controls retinal pigment epithelium development. PLoS Genet 8: pp. e1002757 CrossRef
6. Chen, K, Gao, L, Liu, Y, Zhang, Y, Jiang, DS, Wei, X, Zhu, XH, Zhang, R, Chen, Y, Yang, Q, Kioka, N, Zhang, XD, Li, H (2013) Vinexin-beta protects against cardiac hypertrophy by blocking the Akt-dependent signalling pathway. Basic Res Cardiol 108: pp. 338 CrossRef
7. Dorn, GW (2009) Apoptotic and non-apoptotic programmed cardiomyocyte death in ventricular remodelling. Cardiovasc Res 81: pp. 465-473 CrossRef
8. Dorn, GW (2009) Novel pharmacotherapies to abrogate postinfarction ventricular remodeling. Nat Rev Cardiol 6: pp. 283-291 CrossRef
9. Engelbrecht, AM, Niesler, C, Page, C, Lochner, A (2004) p38 and JNK have distinct regulatory functions on the development of apoptosis during simulated ischaemia and reperfusion in neonatal cardiomyocytes. Basic Res Cardiol 99: pp. 338-350 CrossRef
10. Frangogiannis, NG (2014) The inflammatory response in myocardial injury, repair, and remodelling. Nat Rev Cardiol 11: pp. 255-265 CrossRef
11. Frantz, S, Bauersachs, J, Ertl, G (2009) Post-infarct remodelling: contribution of wound healing and inflammation. Cardiovasc Res 81: pp. 474-481 CrossRef
12. Ghosh, S, Hayden, MS (2008) New regulators of NF-κB in inflammation. Nat Rev Immunol 8: pp. 837-848 CrossRef
13. Gordon, JW, Shaw, JA, Kirshenbaum, LA (2011) Multiple facets of NF-κB in the heart: to be or not to NF-κB. Circ Res 108: pp. 1122-1132 CrossRef
14. Hamid, T, Guo, SZ, Kingery, JR, Xiang, X, Dawn, B, Prabhu, SD (2011) Cardiomyocyte NF-κB p65 promotes adverse remodelling, apoptosis, and endoplasmic reticulum stress in heart failure. Cardiovasc Res 89: pp. 129-138 CrossRef
15. Heusch, G, Libby, P, Gersh, B, Yellon, D, Bohm, M, Lopaschuk, G, Opie, L (2014) Cardiovascular remodelling in coronary artery disease and heart failure. Lancet 383: pp. 1933-1943- 刊物类别：Medicine
- 刊物主题：Medicine & Public Health
Cardiology- 出版者：Springer Berlin / Heidelberg
- ISSN：1435-1803
文摘
Dickkopf-3 (DKK3) is a secreted glycoprotein of the Dickkopf family (DKK1-) that modulates Wnt signalling. DKK3 has been reported to regulate cell development, proliferation, apoptosis, and immune response. However, the functional role of DKK3 in cardiac remodelling after myocardial infarction (MI) has not yet been elucidated. This study aimed to explore the functional significance of DKK3 in the regulation of post-MI remodelling and its underlying mechanisms. MI was induced by surgical left anterior descending coronary artery ligation in transgenic mice expressing cardiac-specific DKK3 and DKK3 knockout (KO) mice as well as their non-transgenic and DKK3+/+ littermates. Our results demonstrated that after MI, mice with DKK3 deficiency had increased mortality, greater infarct size, and exacerbated left ventricular (LV) dysfunction. Significantly, at 1?week post-MI, the hearts of DKK3-KO mice exhibited increased apoptosis, inflammation, and LV remodelling compared with the hearts of their DKK3+/+ littermates. Conversely, DKK3 overexpression led to the opposite phenotype after infarction. Similar results were observed in cultured neonatal rat cardiomyocytes exposed to hypoxia in vitro. Mechanistically, DKK3 promotes cardioprotection by interrupting the ASK1–JNK/p38 signalling cascades. In conclusion, our results indicate that DKK3 protects against the development of MI-induced cardiac remodelling via negative regulation of the ASK1–JNK/p38 signalling pathway. Thus, our study suggests that DKK3 may represent a potential therapeutic target for the treatment of heart failure after MI.