Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The liver peptide hepcidin regulates iron absorption and recycling. Hemojuvelin (HJV) has a key role in hepcidin regulation, and its inactivation causes severe iron overload both in humans and in mice. Membrane HJV (m-HJV) acts as a coreceptor for bone morphogenetic proteins (BMPs), whereas soluble HJV (s-HJV) may down-regulate hepcidin in a competitive way interfering with BMP signaling. s-HJV is decreased by iron in vitro and increased by iron deficiency in vivo. However, the mechanisms regulating the 2 HJV isoforms remain unclear. Here we show that s-HJV originates from a furin cleavage at position 332-335. s-HJV is reduced in the cleavage mutant R335Q as well as in cells treated with a furin inhibitor, and increased in cells overexpressing exogenous furin, but not in cells overexpressing an inactive furin variant. Furin is up-regulated by iron deficiency and hypoxia in association with the stabilization of HIF-1alpha. Increased s-HJV in response to HIF-1alpha occurs during differentiation of murine muscle cells expressing endogenous Hjv. Our data are relevant to the mechanisms that relate iron metabolism to the hypoxic response. The release of s-HJV might be a tissue-specific mechanism, signaling the local iron requests of hypoxic skeletal muscles independently of the oxygen status of the liver.
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PMID:Furin-mediated release of soluble hemojuvelin: a new link between hypoxia and iron homeostasis. 1793 54

This article provides information and a commentary on trials relevant to the pathophysiology, prevention, and treatment of heart failure presented at the annual meeting of the American Heart Association held in Orlando, Florida in 2009. Unpublished reports should be considered as preliminary, as analyses may change in the final publication. Patients with heart failure randomized to high-dose losartan treatment (150 mg) in the HEAAL study had a reduced risk of death or heart failure hospitalization compared with patients in the low-dose (50 mg) group. In FAIR-HF, patients with heart failure and concomitant iron deficiency but without severe anaemia who received iron supplementation therapy demonstrated an improvement in symptoms at 24 weeks compared with placebo. The J-CHF study was too small and was stopped too early to provide definitive evidence about the optimal dose of carvedilol for Japanese patients with heart failure. Results from the HeartMate II study suggest that continuous-flow left ventricular assist devices may offer benefits over pulsatile-flow devices for long-term support in patients with advanced heart failure. In the PACE study, atrial synchronized right ventricular pacing induced adverse effects on left ventricular function compared with atrial synchronized biventricular pacing in patients with standard pacing indications and a normal ejection fraction.
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PMID:Clinical trials update from the American Heart Association meeting 2009: HEAAL, FAIR-HF, J-CHF, HeartMate II, PACE and a meta-analysis of dose-ranging studies of beta-blockers in heart failure. 2008 27