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Pulmonary artery SMCs (PASMCs) were harvested from fetal sheep after partial ligation of the ductus arteriosus in utero (PPHN) and controls. Cell counts were performed daily for 5 days with or without PPAR\u03b3 agonists and ROCK inhibition. PPAR\u03b3 and ROCK protein expression\/activity were measured by Western blot in normal and PPHN PASMCs. We assessed PPAR\u03b3-ROCK interactions by studying the effect of ROCK activation on PPAR\u03b3 activity and PPAR\u03b3 inhibition (siRNA) on ROCK activity and PASMC proliferation. At baseline, PPHN PASMC cell number was increased by 38% above controls on day 5. ROCK protein expression\/activity were increased by 25 and 34% and PPAR\u03b3 protein\/activity decreased by 40 and 50% in PPHN PASMC. ROCK inhibition and PPAR\u03b3 activation restored PPHN PASMC growth to normal values. ROCK inhibition increased PPAR\u03b3 activity by 50% in PPHN PASMC, restoring PPAR\u03b3 activity to normal. In normal PASMCs, ROCK activation decreased PPAR\u03b3 activity and PPAR\u03b3 inhibition increased ROCK activity and cell proliferation, resulting in a PPHN hyperproliferative PASMC phenotype. PPAR\u03b3-ROCK interactions regulate SMC proliferation and contribute to increased PPHN PASMC proliferation and vascular remodeling in PPHN. Restoring normal PPAR\u03b3-ROCK signaling may prevent vascular remodeling and improve outcomes in PPHN.<\/jats:p>","DOI":"10.1152\/ajplung.00271.2013","type":"journal-article","created":{"date-parts":[[2013,12,28]],"date-time":"2013-12-28T03:02:39Z","timestamp":1388199759000},"page":"L299-L308","source":"Crossref","is-referenced-by-count":22,"title":["Peroxisome proliferator activated receptor-\u03b3-Rho-kinase interactions contribute to vascular remodeling after chronic intrauterine pulmonary hypertension"],"prefix":"10.1152","volume":"306","author":[{"given":"Jason","family":"Gien","sequence":"first","affiliation":[{"name":"Department of Neonatology, University of Colorado School of Medicine, Aurora, Colorado;"},{"name":"Pediatric Heart Lung Center, University of Colorado School of Medicine, Aurora, Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy","family":"Tseng","sequence":"additional","affiliation":[{"name":"Department of Neonatology, University of 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