title: A cathepsin D-cleaved 16 kDa form of prolactin mediates postpartum cardiomyopathy.
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 inhibitor 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.
authors.affiliation: Department of Cardiology and Angiology, MHH, 30625 Hannover, Germany. hilfiker.denise@mh-hannover.de
authors.forename: Denise
authors.initials: D
authors.lastname: Hilfiker-Kleiner
authors.forename: Karol
authors.initials: K
authors.lastname: Kaminski
authors.forename: Edith
authors.initials: E
authors.lastname: Podewski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Bonda
authors.forename: Arnd
authors.initials: A
authors.lastname: Schaefer
authors.forename: Karen
authors.initials: K
authors.lastname: Sliwa
authors.forename: Olaf
authors.initials: O
authors.lastname: Forster
authors.forename: Anja
authors.initials: A
authors.lastname: Quint
authors.forename: Ulf
authors.initials: U
authors.lastname: Landmesser
authors.forename: Carola
authors.initials: C
authors.lastname: Doerries
authors.forename: Maren
authors.initials: M
authors.lastname: Luchtefeld
authors.forename: Valeria
authors.initials: V
authors.lastname: Poli
authors.forename: Michael D
authors.initials: MD
authors.lastname: Schneider
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Balligand
authors.forename: Fanny
authors.initials: F
authors.lastname: Desjardins
authors.forename: Aftab
authors.initials: A
authors.lastname: Ansari
authors.forename: Ingrid
authors.initials: I
authors.lastname: Struman
authors.forename: Ngoc Q N
authors.initials: NQ
authors.lastname: Nguyen
authors.forename: Nils H
authors.initials: NH
authors.lastname: Zschemisch
authors.forename: Gunnar
authors.initials: G
authors.lastname: Klein
authors.forename: Gerd
authors.initials: G
authors.lastname: Heusch
authors.forename: Rainer
authors.initials: R
authors.lastname: Schulz
authors.forename: Andres
authors.initials: A
authors.lastname: Hilfiker
authors.forename: Helmut
authors.initials: H
authors.lastname: Drexler
mesh_terms: D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology / Q000627:therapeutic use; D009202:Cardiomyopathies / Q000378:metabolism* / Q000517:prevention & control; D002402:Cathepsin D / Q000097:blood / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D017379:Hypertrophy, Left Ventricular; D007774:Lactation / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism; D009389:Neovascularization, Pathologic; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000097:blood; D049590:Postpartum Period / Q000378:metabolism; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000378:metabolism* / Q000517:prevention & control; D011388:Prolactin / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D011644:Puerperal Disorders / Q000378:metabolism* / Q000517:prevention & control; D050796:STAT3 Transcription Factor / Q000097:blood / Q000235:genetics / Q000378:metabolism*
chemical_list: D008077:Lipoproteins, LDL; D010446:Peptide Fragments; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; C099252:oxidized low density lipoprotein; C503760:prolactin 16-kDa fragment, human; D001971:Bromocriptine; D011388:Prolactin; D002402:Cathepsin D