Loss of caveolin and heme oxygenase expression in severe pulmonary hypertension.
Caveolae are cell plasma membrane microdomains implicated in organizing and concentrating many signaling molecules. In the lung, caveolae are in endothelium, smooth muscle, fibroblasts, and pneumocytes. Caveolin is the main structural protein of caveolae. Caveolin 1 is down-regulated in transformed cells and may be a tumor suppressor protein. Caveolin 2 is coexpressed and hetero-oligomerizes with caveolin 1. Because the cells of the plexiform lesions in severe pulmonary hypertension (PH) are phenotypically altered, we wondered whether these cells lack caveolin. We now demonstrate by immunolocalization that while caveolin is expressed in lung endothelial, smooth-muscle, and alveolar septal cells, its expression is absent or decreased in plexiform lesions and in some muscularized precapillary arterioles. In contrast, Western blot analysis of total lung extracts from patients with severe PH shows no significant reduction in caveolin. Similar to the human lung tissue, a rat model of severe PH demonstrates absent-to-decreased caveolin expression in the complex vascular lesions. Additionally, it appears that caveolin and heme oxygenase 1 (HO-1) [a heat shock protein] are co-expressed since HO-1 expression parallels caveolin expression in vascular lesions. We propose that loss of caveolin expression in the cells of the complex vascular lesions in severe PH reflects the proliferating and apoptosis-resistant nature of these cells.
Pulmonary Hypertension Center, and Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, 4200 E. Ninth Avenue, C272, Denver, CO 80262, USA.
Rosane O D
RO
Achcar
Yoshiki
Y
Demura
Pradeep R
PR
Rai
Laima
L
Taraseviciene-Stewart
Michael
M
Kasper
Norbert F
NF
Voelkel
Carlyne D
CD
Cool
D000328:Adult; D000368:Aged; D000818:Animals; D001160:Arterioles / Q000378:metabolism; D015153:Blotting, Western; D051242:Caveolin 1 / Q000378:metabolism*; D051243:Caveolin 2 / Q000378:metabolism*; D004727:Endothelium / Q000378:metabolism; D005260:Female; D006391:Hemangioma / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism*; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D051381:Rats; D017207:Rats, Sprague-Dawley
D051242:Caveolin 1; D051243:Caveolin 2; D006419:Heme Oxygenase (Decyclizing)