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Cardiomyocyte-specific Estrogen Receptor Alpha Increases Angiogenesis, Lymphangiogenesis and Reduces Fibrosis in the Female Mouse Heart Post-Myocardial Infarction.


ABSTRACT: Experimental studies showed that 17?-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 (ER?) in cardiomyocytes in the setting of myocardial ischemia, we generated transgenic mice with cardiomyocyte-specific overexpression of ER? (ER?-OE) and subjected them to Myocardial Infarction (MI). At the basal level, female and male ER?-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 ER?-OE, but not in female ER?-OE mice. ER?-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 ER?-OE after MI. In conclusion, our study indicates that ER? 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.

SUBMITTER: Mahmoodzadeh S 

PROVIDER: S-EPMC4070011 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Cardiomyocyte-specific Estrogen Receptor Alpha Increases Angiogenesis, Lymphangiogenesis and Reduces Fibrosis in the Female Mouse Heart Post-Myocardial Infarction.

Mahmoodzadeh Shokoufeh S   Leber Joachim J   Zhang Xiang X   Jaisser Frédéric F   Messaoudi Smail S   Morano Ingo I   Furth Priscilla A PA   Dworatzek Elke E   Regitz-Zagrosek Vera V  

Journal of cell science & therapy 20140101 1


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 increase  ...[more]

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