title: Cardiomyocyte-specific Estrogen Receptor Alpha Increases Angiogenesis, Lymphangiogenesis and Reduces Fibrosis in the Female Mouse Heart Post-Myocardial Infarction.
abstract: 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.
authors: Institute of Gender in Medicine and Center for Cardiovascular Research, Charité Universitaetsmedizin, Berlin, Germany.
authors: Shokoufeh
authors: S
authors: Mahmoodzadeh
authors: Institute of Gender in Medicine and Center for Cardiovascular Research, Charité Universitaetsmedizin, Berlin, Germany.
authors: Joachim
authors: J
authors: Leber
authors: Institute of Gender in Medicine and Center for Cardiovascular Research, Charité Universitaetsmedizin, Berlin, Germany.|Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
authors: Xiang
authors: X
authors: Zhang
authors: Inserm, U872, Paris, France.
authors: Frédéric
authors: F
authors: Jaisser
authors: Inserm, U872, Paris, France.
authors: Smail
authors: S
authors: Messaoudi
authors: Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany.
authors: Ingo
authors: I
authors: Morano
authors: Departments of Oncology and Medicine and the Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
authors: Priscilla A
authors: PA
authors: Furth
authors: Institute of Gender in Medicine and Center for Cardiovascular Research, Charité Universitaetsmedizin, Berlin, Germany.
authors: Elke
authors: E
authors: Dworatzek
authors: Institute of Gender in Medicine and Center for Cardiovascular Research, Charité Universitaetsmedizin, Berlin, Germany.
authors: Vera
authors: V
authors: Regitz-Zagrosek
keywords: Angiogenesis; Cardiac fibrosis; Estrogen receptor alpha; Lymphangiogenesis; Myocardial infarction