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)

Peripartum cardiomyopathy (PPCM) is a poorly understood, rare disorder in which left ventricular systolic dysfunction and symptoms of heart failure occur between the last month of pregnancy and the first 5 months postpartum. Recent data suggest that uncontrolled oxidative stress leads to the activation of the prolactin cleaving enzyme cathepsin D that in turn leads to an increase in a cleaved 16 kDa prolactin. This cleaved form that has an angiostatic and proapoptotic role appears to drive the disease by adversely impacting the endothelium and cardiomyocyte. Bromocriptine that reduces the prolactin production by dopamine agonist actions may improve outcomes in patients with peripartum cardiomyopathy by eliminating the cleaved form of prolactin despite the activation of the cleaving enzyme. In limited case reports and proof of concept studies use of bromocriptine in the early stages has been shown to improve outcomes in patients with peripartum cardiomyopathy. However, larger randomized control study is still awaited.
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PMID:Bromocriptine as a new therapeutic agent for peripartum cardiomyopathy. 2270 47

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.
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PMID:Peripartum cardiomyopathy. An update. 2301 76

Peripartum cardiomyopathy (PPCM) is an idiopathic cardiomyopathy presenting with heart failure due to left ventricular systolic dysfunction towards the end of pregnancy or in the months following delivery, where no other cause of heart failure is found. We report a case of a woman with PPCM who developed a critical cardiogenic shock with repeated cardiopulmonary resuscitation. We show for the first time that mechanical circulatory support combined with high-dose bromocriptine therapy to suppress systemic prolactin levels may serve as an effective therapeutic option in patients with fulminant PPCM and cardiogenic shock. Myocardial cathepsin D was overexpressed in our patient underscoring a potential role of cathepsin D-induced cleavage of prolactin in the pathophysiology of PPCM.
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PMID:Complete recovery of fulminant peripartum cardiomyopathy on mechanical circulatory support combined with high-dose bromocriptine therapy. 2874 86