PMID- 24375792
OWN - NLM
STAT- MEDLINE
DCOM- 20140328
LR  - 20211021
IS  - 1522-1504 (Electronic)
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 306
IP  - 3
DP  - 2014 Feb
TI  - Peroxisome proliferator activated receptor-gamma-Rho-kinase interactions contribute 
      to vascular remodeling after chronic intrauterine pulmonary hypertension.
PG  - L299-308
LID - 10.1152/ajplung.00271.2013 [doi]
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma) and Rho-kinase (ROCK) 
      regulate smooth muscle cell (SMC) proliferation and contribute to vascular 
      remodeling in adult pulmonary hypertension. Whether these pathways interact to 
      contribute to the development of vascular remodeling in persistent pulmonary 
      hypertension of the newborn (PPHN) remains unknown. We hypothesized that 
      ROCK-PPARgamma interactions increase SMC proliferation resulting in vascular 
      remodeling in experimental PPHN. 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 PPARgamma 
      agonists and ROCK inhibition. PPARgamma and ROCK protein expression/activity were 
      measured by Western blot in normal and PPHN PASMCs. We assessed PPARgamma-ROCK 
      interactions by studying the effect of ROCK activation on PPARgamma activity and 
      PPARgamma 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 PPARgamma protein/activity 
      decreased by 40 and 50% in PPHN PASMC. ROCK inhibition and PPARgamma activation 
      restored PPHN PASMC growth to normal values. ROCK inhibition increased PPARgamma 
      activity by 50% in PPHN PASMC, restoring PPARgamma activity to normal. In normal 
      PASMCs, ROCK activation decreased PPARgamma activity and PPARgamma inhibition increased 
      ROCK activity and cell proliferation, resulting in a PPHN hyperproliferative 
      PASMC phenotype. PPARgamma-ROCK interactions regulate SMC proliferation and 
      contribute to increased PPHN PASMC proliferation and vascular remodeling in PPHN. 
      Restoring normal PPARgamma-ROCK signaling may prevent vascular remodeling and improve 
      outcomes in PPHN.
FAU - Gien, Jason
AU  - Gien J
AD  - Perinatal Research Facility, 13243 E. 23rd Ave., Mail Stop F441, Aurora, CO 
      80045. jason.gien@ucdenver.edu.
FAU - Tseng, Nancy
AU  - Tseng N
FAU - Seedorf, Gregory
AU  - Seedorf G
FAU - Roe, Gates
AU  - Roe G
FAU - Abman, Steven H
AU  - Abman SH
LA  - eng
GR  - K08 HL102261/HL/NHLBI NIH HHS/United States
GR  - R01 HL068702/HL/NHLBI NIH HHS/United States
GR  - R01 HL068702-05A2/HL/NHLBI NIH HHS/United States
GR  - 5K08HL102261/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20131227
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (PPAR gamma)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
SB  - IM
MH  - Animals
MH  - PPAR gamma/antagonists & inhibitors/biosynthesis/*metabolism
MH  - Persistent Fetal Circulation Syndrome/*metabolism
MH  - Sheep
MH  - Signal Transduction
MH  - rho-Associated Kinases/biosynthesis/*metabolism
PMC - PMC3920199
OTO - NOTNLM
OT  - Rho-kinase (ROCK)
OT  - peroxisome proliferator-activated gamma (PPARgamma)
OT  - persistent pulmonary hypertension of the newborn (PPHN)
OT  - pulmonary artery smooth muscle cells (PASMC)
OT  - vascular remodeling
EDAT- 2014/01/01 06:00
MHDA- 2014/03/29 06:00
PMCR- 2015/02/01
CRDT- 2013/12/31 06:00
PHST- 2013/12/31 06:00 [entrez]
PHST- 2014/01/01 06:00 [pubmed]
PHST- 2014/03/29 06:00 [medline]
PHST- 2015/02/01 00:00 [pmc-release]
AID - ajplung.00271.2013 [pii]
AID - L-00271-2013 [pii]
AID - 10.1152/ajplung.00271.2013 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2014 Feb;306(3):L299-308. doi: 
      10.1152/ajplung.00271.2013. Epub 2013 Dec 27.