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

Med Hypotheses. 2010 Feb;74(2):348-52. doi: 10.1016/j.mehy.2009.08.029. Epub 2009 Sep 11.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiomyopathies / metabolism*
  • Cardiomyopathies / pathology
  • Female
  • Humans
  • Matrix Metalloproteinases / metabolism*
  • Models, Biological
  • Peptide Fragments / metabolism*
  • Pre-Eclampsia / metabolism*
  • Pre-Eclampsia / pathology
  • Pregnancy
  • Pregnancy Complications, Cardiovascular / metabolism*
  • Pregnancy Complications, Cardiovascular / pathology
  • Prolactin / metabolism*
  • Signal Transduction
  • Trophoblasts / metabolism*

Substances

  • Peptide Fragments
  • Prolactin
  • Matrix Metalloproteinases