Altered pulmonary artery endothelial-smooth muscle cell interactions in experimental congenital diaphragmatic hernia.

Pediatr Res

1] Department of Pediatrics, The Pediatric Heart Lung Center, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado [2] Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.

Published: April 2015

Background: Pulmonary hypertension (PH) secondary to vascular remodeling contributes to poor outcomes in congenital diaphragmatic hernia (CDH), however mechanisms responsible are unknown. We hypothesized that pulmonary artery endothelial cell (PAEC) dysfunction contributes to smooth muscle cell (SMC) hyperplasia in experimental CDH.

Methods: PAEC and SMC were isolated from fetal sheep with experimental CDH and controls. SMC growth was assessed alone and with SOD plus catalase and during coculture with control or CDH PAEC with and without ET-1 siRNA transfection. ET-1 protein was measured in PAEC and SMC lysates and supernatant. ROS production was measured in normal and CDH PAECs with and without ET-1 siRNA. PAEC growth and tube formation were measured with SOD plus catalase.

Results: CDH SMC growth was decreased and increased with coculture with CDH PAEC more than control PAEC. Treatment of CDH PAEC with SOD plus catalase or ET-1 siRNA prevented the increase in SMC growth seen with coculture. ET-1 protein was increased in CDH PAEC and SMC. ROS production was increased in CDH PAEC and decreased with ET-1 SiRNA. SOD plus catalase restored CDH PAEC growth and tube formation.

Conclusion: PAEC dysfunction in experimental CDH increases SMC proliferation via ET-1 induced ROS production by PAEC.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4363155PMC
http://dx.doi.org/10.1038/pr.2015.13DOI Listing

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Altered pulmonary artery endothelial-smooth muscle cell interactions in experimental congenital diaphragmatic hernia.

Pediatr Res

April 2015

1] Department of Pediatrics, The Pediatric Heart Lung Center, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado [2] Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.

Background: Pulmonary hypertension (PH) secondary to vascular remodeling contributes to poor outcomes in congenital diaphragmatic hernia (CDH), however mechanisms responsible are unknown. We hypothesized that pulmonary artery endothelial cell (PAEC) dysfunction contributes to smooth muscle cell (SMC) hyperplasia in experimental CDH.

Methods: PAEC and SMC were isolated from fetal sheep with experimental CDH and controls.

View Article and Find Full Text PDF

Decreased lung vascular growth and pulmonary hypertension contribute to poor outcomes in congenital diaphragmatic hernia (CDH). Mechanisms that impair angiogenesis in CDH are poorly understood. We hypothesize that decreased vessel growth in CDH is caused by pulmonary artery endothelial cell (PAEC) dysfunction with loss of a highly proliferative population of PAECs (HP-PAEC).

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