title: Pulmonary arterial hypertension and left-sided heart disease in sickle cell disease: clinical characteristics and association with soluble adhesion molecule expression.
abstract: Pulmonary hypertension (PH), a risk factor for mortality in sickle cell disease (SCD), has pathologic features of both pulmonary arterial hypertension (PAH) and PH related to left-sided heart disease (LHD) suggesting a link between these two entities. We hypothesized that both are characterized by endothelial dysfunction and increased adhesion molecule expression. SCD patients and normal volunteers underwent a screening questionnaire, echocardiogram, and blood donation for preparation of platelet-poor plasma. PAH was defined as a tricuspid regurgitant jet (TRJ) velocity > or =2.5 m/sec and/or the presence of isolated right ventricular hypertrophy or decreased systolic function. LHD was defined as either left-sided systolic/diastolic dysfunction or significant valvular disease. Plasma vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), P- and E-selectin, nitric oxide (NO(x)), erythropoietin, and vascular endothelial growth factor (VEGF) levels were assayed by enzyme-linked immunoassay. Forty-three percent of sickle cell anemia (HbSS) and 28% of hemoglobin SC disease (HbSC) disease patients had PAH. Additionally, 10-15% of SCD patients had LHD. VCAM-1 levels were significantly increased in HbSS patients compared with HbSC patients and normal volunteers. VCAM-1 and P-selectin levels correlated positively with TRJ velocity in HbSS patients (r = 0.45, P = 0.03, r = 0.2, P = 0.05, respectively). ICAM-1, E-selectin, NO(x), erythropoietin, and VEGF levels were similar across subject groups. PH is common in SCD and, at times, due to LHD. Increased VCAM-1 and P-selectin expression was associated with TRJ elevation regardless of etiology suggesting a similar effect on endothelial gene expression and possibly providing a pathologic link between PAH and PH related to LHD in SCD.
authors.affiliation: The Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA. klingon@bu.edu
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Klings
authors.forename: Demedrick
authors.initials: D
authors.lastname: Anton Bland
authors.forename: Dara
authors.initials: D
authors.lastname: Rosenman
authors.forename: Stephanie
authors.initials: S
authors.lastname: Princeton
authors.forename: Adam
authors.initials: A
authors.lastname: Odhiambo
authors.forename: Guihua
authors.initials: G
authors.lastname: Li
authors.forename: Sheilah A
authors.initials: SA
authors.lastname: Bernard
authors.forename: Martin H
authors.initials: MH
authors.lastname: Steinberg
authors.forename: Harrison W
authors.initials: HW
authors.lastname: Farber
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications / Q000453:epidemiology / Q000378:metabolism*; D005260:Female; D006331:Heart Diseases / Q000150:complications / Q000453:epidemiology / Q000378:metabolism*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000453:epidemiology / Q000378:metabolism*; D008297:Male; D019007:P-Selectin / Q000378:metabolism*; D012995:Solubility; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D019007:P-Selectin; D019010:Vascular Cell Adhesion Molecule-1