Prolactin fragmentation by trophoblastic matrix metalloproteinases as a possible contributor to peripartum cardiomyopathy and pre-eclampsia

Reuwer, Anne Q.; Reuwer, Paul J.H.M.; van der Post, Joris A.; Cramer, Maarten J.; Kastelein, John J.P.; Twickler, Marcel Th. B.

doi:10.1016/J.MEHY.2009.08.029

Title

Prolactin fragmentation by trophoblastic matrix metalloproteinases as a possible contributor to peripartum cardiomyopathy and pre-eclampsia

Author

Reuwer, Anne Q.

Reuwer, Paul J.H.M.

van der Post, Joris A.

Cramer, Maarten J.

Kastelein, John J.P.

Twickler, Marcel Th. B.

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 in 16 kDa 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 16 kDa 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. (C) 2009 Elsevier Ltd. All rights reserved.

Language

English

Source (journal)

Medical hypotheses. - Edinburgh

Publication

Edinburgh : 2010

ISSN

0306-9877

DOI

10.1016/J.MEHY.2009.08.029

Volume/pages

74 :2 (2010) , p. 348-352