title: Enhanced caveolin-1 expression in smooth muscle cells: Possible prelude to neointima formation.
abstract: OBJECTIVE
  To study the genesis of neointima formation in pulmonary hypertension (PH), we investigated the role of caveolin-1 and related proteins.
  
  
  METHODS
  Male Sprague Dawley rats were given monocrotaline (M, 40 mg/kg) or subjected to hypobaric hypoxia (H) to induce PH. Another group was given M and subjected to H to accelerate the disease process (M + H). Right ventricular systolic pressure, right ventricular hypertrophy, lung histology for medial hypertrophy and the presence of neointimal lesions were examined at 2 and 4 wk. The expression of caveolin-1 and its regulatory protein peroxisome proliferator-activated receptor (PPAR) γ, caveolin-2, proliferative and anti-apoptotic factors (PY-STAT3, p-Erk, Bcl-xL), endothelial nitric oxide synthase (eNOS) and heat shock protein (HSP) 90 in the lungs were analyzed, and the results from M + H group were compared with the controls, M and H groups. Double immunofluorescence technique was used to identify the localization of caveolin-1 in pulmonary arteries in rat lungs and in human PH lung tissue.
  
  
  RESULTS
  In the M + H group, PH was more severe compared with M or H group. In the 4 wk M+H group, several arteries with reduced caveolin-1 expression in endothelial layer coupled with an increased expression in smooth muscle cells (SMC), exhibited neointimal lesions. Neointima was present only in the arteries exhibiting enhanced caveolin-1 expression in SMC. Lung tissue obtained from patients with PH also revealed neointimal lesions only in the arteries exhibiting endothelial caveolin-1 loss accompanied by an increased caveolin-1 expression in SMC. Reduction in eNOS and HSP90 expression was present in the M groups (2 and 4 wk), but not in the M + H groups. In both M groups and in the M + H group at 2 wk, endothelial caveolin-1 loss was accompanied by an increase in PPARγ expression. In the M + H group at 4 wk, increase in caveolin-1 expression was accompanied by a reduction in the PPARγ expression. In the H group, there was neither a loss of endothelial caveolin-1, eNOS or HSP90, nor an increase in SMC caveolin-1 expression; or any alteration in PPARγ expression. Proliferative pathways were activated in all experimental groups.
  
  
  CONCLUSIONS
  Enhanced caveolin-1 expression in SMC follows extensive endothelial caveolin-1 loss with subsequent neointima formation. Increased caveolin-1 expression in SMC, thus, may be a prelude to neointima formation.
authors.affiliation: Jing Huang, Michael H Gewitz, Rajamma Mathew, Department of Pediatrics, Maria Fareri Children's Hospital, New York Medical College, Valhalla, NY 10595, United States.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Jing Huang, Michael H Gewitz, Rajamma Mathew, Department of Pediatrics, Maria Fareri Children's Hospital, New York Medical College, Valhalla, NY 10595, United States.
authors.forename: John H
authors.initials: JH
authors.lastname: Wolk
authors.affiliation: Jing Huang, Michael H Gewitz, Rajamma Mathew, Department of Pediatrics, Maria Fareri Children's Hospital, New York Medical College, Valhalla, NY 10595, United States.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Gewitz
authors.affiliation: Jing Huang, Michael H Gewitz, Rajamma Mathew, Department of Pediatrics, Maria Fareri Children's Hospital, New York Medical College, Valhalla, NY 10595, United States.
authors.forename: James E
authors.initials: JE
authors.lastname: Loyd
authors.affiliation: Jing Huang, Michael H Gewitz, Rajamma Mathew, Department of Pediatrics, Maria Fareri Children's Hospital, New York Medical College, Valhalla, NY 10595, United States.
authors.forename: James
authors.initials: J
authors.lastname: West
authors.affiliation: Jing Huang, Michael H Gewitz, Rajamma Mathew, Department of Pediatrics, Maria Fareri Children's Hospital, New York Medical College, Valhalla, NY 10595, United States.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Austin
authors.affiliation: Jing Huang, Michael H Gewitz, Rajamma Mathew, Department of Pediatrics, Maria Fareri Children's Hospital, New York Medical College, Valhalla, NY 10595, United States.
authors.forename: Rajamma
authors.initials: R
authors.lastname: Mathew
keywords: Endothelial cells; Neointima; Pulmonary hypertension; Smooth muscle cells