Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Prolactin fragmentation by trophoblastic matrix metalloproteinases as a possible contributor to peripartum cardiomyopathy and pre-eclampsia. 1974 90

Peripartum cardiomyopathy (PPCM) is a rare disease of the heart muscle that affects women with previously unknown heart diseases during pregnancy or in the first months after delivery. Cardinal symptoms are dyspnoea and fluid retention. However, tachycardia, cardiogenic thromboembolism and other clinical signs of cardiac dysfunction may also herald this uncommon cause of heart failure. The estimated incidence of PPCM shows large regional variations: in Europe and the United States it is between 1:2000 and 1:4000. The markedly higher incidence rates observed in Haitian or South African women (up to 1:300) suggest that genetic or environmental factors may play a pathogenetic role. However, the underlying aetiology of PPCM still is unclear. Besides genetic susceptibility an abnormal autoimmune response against cardiac tissue components, viral infections or an irregular activity of cathepsin D generating a potentially cardio-toxic splice variant of prolactin have been discussed. New therapeutic strategies as immune modulation or prolactin inhibition were therefore suggested, but are not yet established. Treatment strategies focus on the standard therapies for heart failure and its complications. During pregnancy heart failure therapy is limited to substances without fetotoxic effects. But even with optimal heart failure therapy the course of the disease exhibits large variations ranging from full recovery to deterioration of heart function and even early cardiac death. This review cumulates the current knowledge on PPCM and aims to raise awareness for this rare and potentially life-threatening disorder amongst all medical professionals involved in the care for pregnant women.
 ...
PMID:Peripartum cardiomyopathy. An update. 2301 76