title: Dysregulation of ubiquitin-proteasome pathway and apolipoprotein A metabolism in sickle cell disease-related pulmonary arterial hypertension.
abstract: 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.
authors.affiliation: State University of New York Downstate Medical Center, Brooklyn, New York, USA.
authors.forename: Fatima
authors.initials: F
authors.lastname: Anjum
authors.affiliation: State University of New York Downstate Medical Center, Brooklyn, New York, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Lazar
authors.affiliation: State University of New York Downstate Medical Center, Brooklyn, New York, USA.
authors.forename: James
authors.initials: J
authors.lastname: Soh
authors.affiliation: Quest Diagnostics, Nichols Institute, San Juan Capistrano, California, USA.
authors.forename: Maher
authors.initials: M
authors.lastname: Albitar
authors.affiliation: State University of New York Downstate Medical Center, Brooklyn, New York, USA.
authors.forename: Satish
authors.initials: S
authors.lastname: Gowda
authors.affiliation: State University of New York Downstate Medical Center, Brooklyn, New York, USA ; Veterans Affairs Medical Center, Brooklyn, New York, USA.
authors.forename: M Mahmood
authors.initials: MM
authors.lastname: Hussain
authors.affiliation: State University of New York Downstate Medical Center, Brooklyn, New York, USA ; Veterans Affairs Medical Center, Brooklyn, New York, USA.
authors.forename: Raj
authors.initials: R
authors.lastname: Wadgaonkar
keywords: apolipoprotein A (Apo-A); pulmonary arterial hypertension (PAH); sickle cell disease (SCD); ubiquitin-proteasome pathway (UPP)