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This Article Full Text Full Text (PDF) Supplemental Figures and Tables All Versions of this Article: 295/6/L1028    most recent 90449.2008v1 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 Google Scholar Articles by Majka, S. M. Articles by West, J. PubMed PubMed Citation Articles by Majka, S. M. Articles by West, J.

Evidence for cell fusion is absent in vascular lesions associated with pulmonary arterial hypertension

¹Cardiovascular Pulmonary Research, ²Department of Medicine, ³Gates Center for Regenerative Medicine and Stem Cell Biology, ⁵Department of Medicine, Medical Oncology, Cancer Center, and ⁶Department of Pediatrics, Division of Pulmonary, and Critical Care Medicine, University of Colorado Denver, Aurora, Colorado; and ⁷Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University, Nashville, Tennessee

Submitted 19 August 2008 ; accepted in final form 15 October 2008

Pulmonary arterial hypertension (PAH) is a fatal disease associated with severe remodeling of the large and small pulmonary arteries. Increased accumulation of inflammatory cells and apoptosis-resistant cells are contributing factors. Proliferative apoptosis-resistant cells expressing CD133 are increased in the circulation of PAH patients. Circulating cells can contribute to tissue repair via cell fusion and heterokaryon formation. We therefore hypothesized that in the presence of increased leukocytes and CD133-positive (CD133^pos) cells in PAH lung tissue, cell fusion and resulting genomic instability could account for abnormal cell proliferation and the genesis of vascular lesions. We performed analyses of CD45/CD133 localization, cell fusion, and proliferation during late-stage PAH in human lung tissue from control subjects and subjects with idiopathic (IPAH) and familial (FPAH) PAH. Localization, proliferation, and quantitation of cell populations in individual patients were performed by immunolocalization. The occurrence of cellular fusion in vascular lesions was analyzed in lung tissue by fluorescence in situ hybridization. We found the accumulation of CD45^pos leukocytic cells in the tissue parenchyma and perivascular regions in PAH patients and less frequently observed myeloid cells (CD45/CD11b). CD133^pos cells were detected in occlusive lesions and perivascular areas in those with PAH and were more numerous in those with IPAH lesions than in FPAH lesions. Cells coexpressing CD133 and smooth muscle -actin were occasionally observed in occlusive lesions and perivascular areas. Proliferating cells were more prominent in IPAH lesions and colocalized with CD45 or CD133. We found no evidence of increased ploidy to suggest cell fusion. Taken together, these data suggest that abnormal lesion formation in PAH occurs in the absence of cell fusion.

vascular remodeling; chromosomal aneusomy; chimerism; cell fusion