Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P62988 (Ubiquitin)
 4,326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pulmonary arterial hypertension (PAH) is a major complication of sickle cell disease (SCD). Low levels of apolipoprotein A1 (Apo-A1) have been implicated in the development of PAH in SCD. We speculate that lower levels of Apo-A1 are related to dysregulation of the ubiquitin-proteasome pathway (UPP). Of 36 recruited patients with SCD, 14 were found to have PAH on the basis of right heart catheterization. Levels of Apo-A1 and Apo-B, polyubiquitin, total protease, and specific and normalized activity of chymotrypsin-like, trypsin-like, and caspase-like proteases in plasma were measured. Levels of Apo-A1 were found to be lower and polyubiquitin levels were found to be significantly higher in the PAH group ([Formula: see text]) in SCD. Apo-A levels were inversely correlated with polyubiquitin levels ([Formula: see text], [Formula: see text]). These results indicate that lower levels of Apo-A1 in SCD patients with PAH are likely related to enhance degradation by UPP, potentially contributing to pulmonary vascular pathology. These findings may provide significant insight in identifying suitable therapeutic targets in these patients.
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PMID:Dysregulation of ubiquitin-proteasome pathway and apolipoprotein A metabolism in sickle cell disease-related pulmonary arterial hypertension. 2500