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Blood, 29 January 2009, Vol. 113, No. 5, pp. 1122-1128. Prepublished online as a Blood First Edition Paper on November 20, 2008; DOI 10.1182/blood-2008-03-142604. This Article Full Text Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2008-03-142604v1 113/5/1122    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yuditskaya, S. Articles by Kato, G. J. Search for Related Content PubMed PubMed Citation Articles by Yuditskaya, S. Articles by Kato, G. J. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS, IRON, AND ERYTHROPOIESIS Proteomic identification of altered apolipoprotein patterns in pulmonary hypertension and vasculopathy of sickle cell disease Susan Yuditskaya1, Ashaunta Tumblin1, Gerard T. Hoehn2, Guanghui Wang2, Steven K. Drake2, Xiuli Xu1, Saixia Ying3, Amy H. Chi1, Alan T. Remaley1, Rong-Fong Shen4, Peter J. Munson3, Anthony F. Suffredini2, and Gregory J. Kato1,2 1 Pulmonary and Vascular Medicine Branch, National Heart, Lung and Blood Institute, 2 Critical Care Medicine Department, Clinical Center, 3 Center for Information Technology, and 4 Proteomics Core Facility, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD Pulmonary arterial hypertension (PAH) is emerging as a major complication and independent risk factor for death among adults with sickle cell disease (SCD). Using surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF MS), we searched for biomarkers of PAH in plasma specimens from 27 homozygous sickle cell anemia (HbSS) patients with PAH and 28 without PAH. In PAH patients, analysis consistently showed lower abundance of a 28.1-kDa peak (P < .001), identified by high-resolution mass spectrometry as the oxidant-scavenging protein apolipoprotein A-I (apoA-I), which correlated with clinical assays of apoA-I (r = .58, P < .001) and high-density lipoprotein (HDL) levels (r = .50, P = .001). Consistent with endothelial dysfunction that may mediate this effect in PAH, HbSS patients with lower apoA-I levels also displayed impaired vasodilatory responses to acetylcholine (mean ± SEM, 189% ± 34% [n = 13] vs 339% ± 51% [n = 13], P < .001). As a group, patients with SCD demonstrated significantly lower apoA-I levels than African-American control subjects. The PAH cohort was further characterized by high levels of apolipoproteins A-II and B and serum amyloid A, and low levels of haptoglobin dimers and plasminogen. These results imply a relationship of apolipoproteins to the development of PAH vasculopathy in SCD, potentially involving an unexpected mechanistic parallel to atherosclerosis, another proliferative vasculopathy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. B. Ware Clinical Year in Review I: Interstitial Lung Disease, Pulmonary Vascular Disease, Pulmonary Infections, and Cardiopulmonary Exercise Testing and Pulmonary Rehabilitation Proceedings of the ATS, September 15, 2009; 6(6): 487 - 493. [Full Text] [PDF] G. J. Kato and M. T. Gladwin Evolution of Novel Small-Molecule Therapeutics Targeting Sickle Cell Vasculopathy JAMA, December 10, 2008; 300(22): 2638 - 2646. [Abstract] [Full Text] [PDF]

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