Cardiomyocyte-specific Estrogen Receptor Alpha Increases Angiogenesis,Lymphangiogenesis and Reduces Fibrosis in the Female Mouse Heart Post-Myocardial InfarctionShokoufeh Mahmoodzadeh1*#, Joachim Leber1#, Xiang Zhang1,2#, Frédéric Jaisser3, Smail Messaoudi3, Ingo Morano4, Priscilla A Furth5, Elke Dworatzek1 and Vera Regitz-Zagrosek1
- *Corresponding Author:
- Shokoufeh Mahmoodzadeh
Institute of Gender in Medicine
Center for Cardiovascular Research
Hessische Str. 3-4, 10115 Berlin, Germany
Tel: +49 (0)30 450 525 287
Fax: +49 (0)30 450 525 943
E-mail: [email protected]
Received date: December 29, 2013; Accepted date: January 27, 2014; Published date: January 30, 2014
Citation: Mahmoodzadeh S, Leber J, Zhang X, Jaisser F, Messaoudi S, et al. (2014) Cardiomyocyte-specific Estrogen Receptor Alpha Increases Angiogenesis, Lymphangiogenesis and Reduces Fibrosis in the Female Mouse Heart Post-Myocardial Infarction. J Cell Sci Ther 5:153. doi: 10.4172/2157-7013.1000153
Copyright: © 2014 Mahmoodzadeh S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Experimental studies showed that 17β-estradiol (E2) and activated Estrogen Receptors (ER) protect the heart from ischemic injury. However, the underlying molecular mechanisms are not well understood. To investigate the role of ER-alpha (ERα) in cardiomyocytes in the setting of myocardial ischemia, we generated transgenic mice with cardiomyocyte-specific overexpression of ERα (ERα-OE) and subjected them to Myocardial Infarction (MI). At the basal level, female and male ERα-OE mice showed increased Left Ventricular (LV) mass, LV volume and cardiomyocyte length. Two weeks after MI, LV volume was significantly increased and LV wall thickness decreased in female and male WT-mice and male ERα-OE, but not in female ERα-OE mice. ERα-OE enhanced expression of angiogenesis and lymphangiogenesis markers (Vegf, Lyve-1), and neovascularization in the peri-infarct area in both sexes. However, attenuated level of fibrosis and higher phosphorylation of JNK signaling pathway could be detected only in female ERα-OE after MI. In conclusion, our study indicates that ERα protects female mouse cardiomyocytes from the sequelae of ischemia through induction of neovascularization in a paracrine fashion and impaired fibrosis, which together may contribute to the attenuation of cardiac remodelling.