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

Acker SN, Seedorf GJ, Abman SH, Nozik-Grayck E, Kuhn K, Partrick DA, Gien J - Pediatr. Res. (2015)

Bottom Line: ROS production was increased in CDH PAEC and decreased with ET-1 SiRNA.SOD plus catalase restored CDH PAEC growth and tube formation.PAEC dysfunction in experimental CDH increases SMC proliferation via ET-1 induced ROS production by PAEC.

View Article: PubMed Central - PubMed

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

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

PASMC growth in experimental CDH. In comparison with cells from control animals, PASMC from right CDH animals grew significantly slower. PASMC from left grew slower than those from the right in CDH animals (Panel A). The addition of SOD plus catalase had no effect on the growth of PASMC from either control or right CDH PASMC (Panel B; p not significant for all comparisons noted)). Bars represent standard error from the mean. Bosentan treatment had no effect on PASMC growth from either control or right CDH PASMC (Panel C; p not significant for all comparisons noted). *p<0.05.
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Figure 1: PASMC growth in experimental CDH. In comparison with cells from control animals, PASMC from right CDH animals grew significantly slower. PASMC from left grew slower than those from the right in CDH animals (Panel A). The addition of SOD plus catalase had no effect on the growth of PASMC from either control or right CDH PASMC (Panel B; p not significant for all comparisons noted)). Bars represent standard error from the mean. Bosentan treatment had no effect on PASMC growth from either control or right CDH PASMC (Panel C; p not significant for all comparisons noted). *p<0.05.

Mentions: In comparison to control PASMCs, CDH PASMC growth is decreased by 24% on the right and 58% on the left (p<0.05; FIGURE 1a). The addition of SOD plus catalase did not affect the growth of PASMC from either control or right CDH pulmonary arteries (FIGURE 1b). Bosentan had no effect on the growth of PASMC from control or right CDH pulmonary arteries (FIGURE 1c).


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

Acker SN, Seedorf GJ, Abman SH, Nozik-Grayck E, Kuhn K, Partrick DA, Gien J - Pediatr. Res. (2015)

PASMC growth in experimental CDH. In comparison with cells from control animals, PASMC from right CDH animals grew significantly slower. PASMC from left grew slower than those from the right in CDH animals (Panel A). The addition of SOD plus catalase had no effect on the growth of PASMC from either control or right CDH PASMC (Panel B; p not significant for all comparisons noted)). Bars represent standard error from the mean. Bosentan treatment had no effect on PASMC growth from either control or right CDH PASMC (Panel C; p not significant for all comparisons noted). *p<0.05.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4363155&req=5

Figure 1: PASMC growth in experimental CDH. In comparison with cells from control animals, PASMC from right CDH animals grew significantly slower. PASMC from left grew slower than those from the right in CDH animals (Panel A). The addition of SOD plus catalase had no effect on the growth of PASMC from either control or right CDH PASMC (Panel B; p not significant for all comparisons noted)). Bars represent standard error from the mean. Bosentan treatment had no effect on PASMC growth from either control or right CDH PASMC (Panel C; p not significant for all comparisons noted). *p<0.05.
Mentions: In comparison to control PASMCs, CDH PASMC growth is decreased by 24% on the right and 58% on the left (p<0.05; FIGURE 1a). The addition of SOD plus catalase did not affect the growth of PASMC from either control or right CDH pulmonary arteries (FIGURE 1b). Bosentan had no effect on the growth of PASMC from control or right CDH pulmonary arteries (FIGURE 1c).

Bottom Line: ROS production was increased in CDH PAEC and decreased with ET-1 SiRNA.SOD plus catalase restored CDH PAEC growth and tube formation.PAEC dysfunction in experimental CDH increases SMC proliferation via ET-1 induced ROS production by PAEC.

View Article: PubMed Central - PubMed

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

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus