title: Pathogenesis and evolution of plexiform lesions in pulmonary hypertension associated with scleroderma and human immunodeficiency virus infection.
abstract: Patients with primary pulmonary hypertension develop vascular lesions characterized by proliferated blood channels, the so-called plexiform lesions. These lesions are often associated with concentric intimal obliteration of pulmonary vessels. We report that the lungs of three patients with scleroderma-associated pulmonary hypertension showed a predominance of obliterative-concentric lesions, with relatively few plexiform or combined lesions. In contrast, plexiform lesions predominated in the lungs obtained from three patients with human immunodeficiency virus (HIV)-associated pulmonary hypertension; pure obliterative-concentric lesions were infrequent. Both plexiform and concentric obliterative lesions stained strongly positive for the endothelial cell marker factor VIII-related antigen. Muscle-specific actin immunostaining highlighted the smooth muscle cells of the tunica media of plexiform vessels, but not the luminal layers of the concentric-obliterative lesions. Proliferating cells, as determined by immunostaining with the MIB-1 antibody, were only detected in the plexiform vascular lesions. We postulate that concentric-obliterative lesions and plexiform lesions are temporally and etiologically related. A scaffolding of proliferating endothelial cells could be the common denominator of both lesions. Our hypothesis that there exists a chronological continuum, proceeding from early, proliferative plexiform lesions to late, nonproliferative concentric-obliterative lesions in primary and secondary pulmonary hypertension, may lead to better targeted treatment strategies and disease classification.
authors.affiliation: Department of Pathology, University of Colorado Health Sciences Center, Denver 80262, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Cool
authors.forename: D
authors.initials: D
authors.lastname: Kennedy
authors.forename: N F
authors.initials: NF
authors.lastname: Voelkel
authors.forename: R M
authors.initials: RM
authors.lastname: Tuder
mesh_terms: D000199:Actins / Q000032:analysis; D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D002455:Cell Division; D004730:Endothelium, Vascular / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D005169:Factor VIII / Q000032:analysis; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000276:immunology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000276:immunology / Q000473:pathology*; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D017493:Leukocyte Common Antigens / Q000032:analysis; D008168:Lung / Q000098:blood supply / Q000737:chemistry / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000473:pathology; D012595:Scleroderma, Systemic / Q000150:complications* / Q000276:immunology; D000097382:CD68 Molecule
chemical_list: D000199:Actins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017252:CD3 Complex; D005169:Factor VIII; D019394:Ki-67 Antigen; D017493:Leukocyte Common Antigens; C067980:CD68 antigen, human; D000097382:CD68 Molecule