This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Pulmonary disease is an important cause of morbidity and mortality in sickle cell disease (SCD). Chronic sickle cell lung disease is characterized by pulmonary hypertension (PH) and right-sided congestive heart failure which may be present in up to 60%, often asymptomatically. The etiology of PH in SCD is unclear but appears linked to recurrent episodes of acute chest syndrome (ACS). Study of etiological factors responsible for development of PH in SCD is important as PH represents an independent risk factor for death in this population. We hypothesize that extra-erthyrocytic genetic factors act via endothelial dysfunction to play a role in the development of PH in SCD. The goal of this study is to determine the prevalence of PH in a population of SCD patients and to use this patient group to determine genetic factors responsible for development of chronic pulmonary disease in SCD. Experimental Design: We will use screening questionnaires and subsequent ECHOcardiograms on 100 hemoglobin (Hb) SS patients of the Sickle Cell Clinic at Boston Medical Center and 20 Hb AA racially matched volunteers without a history of cardiopulmonary disease. Peripheral blood samples will be obtained from all patients studied and platelet poor plasma will be prepared. Protein levels of endothelin-1, nitric oxide, vascular cell adhesion molecule-1, P- and E-selectin will be measured by ELISA. Additionally, cDNA will be generated from blood samples for SNP analysis. Protein expression profiles of plasma will be determined by protocols established by the Proteomics Center at Boston University.
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