title: Different patterns of endothelial cell activation in renal and pulmonary vascular disease in scleroderma.
abstract: Abnormal endothelial cell function is implicated in the development of scleroderma, and in major life-threatening complications of the disease. The nature of the stimulus leading to abnormal endothelial cell function in scleroderma, scleroderma renal crisis, and scleroderma-associated pulmonary hypertension was investigated by measurement of soluble adhesion molecules, shed by activated endothelial cells, in sera from patients with these conditions. In scleroderma renal crisis, mean levels of soluble E-selectin (p < 0.05 limited scleroderma, p < 0.0001 diffuse scleroderma), sVCAM-1 (soluble vascular cell adhesion molecule-1) (p < 0.05 limited scleroderma, p < 0.05 diffuse scleroderma), and sICAM-1 (soluble intercellular adhesion molecule-1) (p < 0.0001 limited scleroderma, p < 0.0001 diffuse scleroderma) were raised, supporting a model of endothelial cell activation in this complication. Evidence for endothelial cell activation in scleroderma-associated pulmonary hypertension was inconsistent, with normal sE-selectin and normal sVCAM-1 in sera from patients with limited scleroderma and pulmonary hypertension. The endothelial cell phenotype in scleroderma-associated pulmonary hypertension may resemble that of unstimulated cells. The pulmonary vascular and renal vascular lesions associated with scleroderma may arise by distinct pathogenic mechanisms.
authors.affiliation: Department of Academic Rheumatology, Royal Free Hospital and School of Medicine, London.
authors.forename: R J
authors.initials: RJ
authors.lastname: Stratton
authors.forename: J G
authors.initials: JG
authors.lastname: Coghlan
authors.forename: J D
authors.initials: JD
authors.lastname: Pearson
authors.forename: A
authors.initials: A
authors.lastname: Burns
authors.forename: P
authors.initials: P
authors.lastname: Sweny
authors.forename: D J
authors.initials: DJ
authors.lastname: Abraham
authors.forename: C M
authors.initials: CM
authors.lastname: Black
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000097:blood*; D019040:E-Selectin / Q000097:blood; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000378:metabolism; D006977:Hypertension, Renal / Q000209:etiology / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D011928:Raynaud Disease / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000150:complications* / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
chemical_list: D015815:Cell Adhesion Molecules; D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1