title: Prolactin fragmentation by trophoblastic matrix metalloproteinases as a possible contributor to peripartum cardiomyopathy and pre-eclampsia.
abstract: Although peripartum cardiomyopathy (PPCM) is a rare disease, it has very serious consequences for both mother and child. No single cause has been held responsible for the pathogenesis. Recent studies have indicated that increased proteolytic cathepsin D activity in cardiomyocytes results in16kDa prolactin fragments with anti-angiogenic and apoptotic properties, which may contribute to the development of PPCM. In support of these findings, lowering full-length prolactin production by bromocriptine therapy has been reported to prevent impairment of cardiac function. PPCM is associated with an increased co-existence of pre-eclampsia, however, a causal relationship has been disputed. We hypothesize that the pathophysiology of PPCM and pre-eclampsia share the same molecular pathway: increased activity of trophoblastic matrix metalloproteinases at the feto-maternal interface may aggravate proteolysis of full-length prolactin, and subsequently the formed 16kDa prolactin fragments may contribute to deterioration of PPCM and pre-eclampsia. Therefore, we argue that it may be worthwhile to explore wether prolactin inhibition is not only beneficial for PPCM patients, but also for the much more prevalent pre-eclamptic women.
authors.affiliation: Department of Vascular Medicine of the Academic Medical Center Amsterdam, The Netherlands. A.Q.Reuwer@amc.uva.nl
authors.forename: Anne Q
authors.initials: AQ
authors.lastname: Reuwer
authors.forename: Paul J H M
authors.initials: PJ
authors.lastname: Reuwer
authors.forename: Joris A
authors.initials: JA
authors.lastname: van der Post
authors.forename: Maarten J
authors.initials: MJ
authors.lastname: Cramer
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Marcel Th B
authors.initials: MT
authors.lastname: Twickler
mesh_terms: D009202:Cardiomyopathies / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008954:Models, Biological; D010446:Peptide Fragments / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000378:metabolism* / Q000473:pathology; D011388:Prolactin / Q000378:metabolism*; D015398:Signal Transduction; D014327:Trophoblasts / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D011388:Prolactin; D020782:Matrix Metalloproteinases