Author/Authors :
Denise Hilfiker-Kleiner، نويسنده , , Karol Kaminski، نويسنده , , Edith Podewski، نويسنده , , Tomasz Bonda، نويسنده , , Arnd Schaefer، نويسنده , , Karen Sliwa، نويسنده , , Olaf Forster، نويسنده , , Anja Quint، نويسنده , , Ulf Landmesser، نويسنده , , Carola Doerries، نويسنده , , Maren Luchtefeld، نويسنده , , Valeria Poli، نويسنده , , Michael D. Schneider، نويسنده , , Jean-Luc Balligand، نويسنده , , Fanny Desjardins، نويسنده , , Aftab Ansari، نويسنده , , Ingrid Struman، نويسنده , , Ngoc Q.N. Nguyen، نويسنده , , Nils H. Zschemisch، نويسنده , , Gunnar Klein، نويسنده , , et al.، نويسنده ,
Abstract :
Postpartum cardiomyopathy (PPCM) is a disease of unknown etiology and exposes women to high risk of mortality after delivery. Here, we show that female mice with a cardiomyocyte-specific deletion of stat3 develop PPCM. In these mice, cardiac cathepsin D (CD) expression and activity is enhanced and associated with the generation of a cleaved antiangiogenic and proapoptotic 16 kDa form of the nursing hormone prolactin. Treatment with bromocriptine, an inhibitior of prolactin secretion, prevents the development of PPCM, whereas forced myocardial generation of 16 kDa prolactin impairs the cardiac capillary network and function, thereby recapitulating the cardiac phenotype of PPCM. Myocardial STAT3 protein levels are reduced and serum levels of activated CD and 16 kDa prolactin are elevated in PPCM patients. Thus, a biologically active derivative of the pregnancy hormone prolactin mediates PPCM, implying that inhibition of prolactin release may represent a novel therapeutic strategy for PPCM.
