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1 Department of Pediatrc Pulmonary Medicine, University of Colorado Health Sciences Center, Denver, Colorado, USA
2 Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
3 Department of Pediatric Cardiology, University of Colorado Health Sciences Center, Denver, Colorado, USA
4 Department of Neonatology, University of Colorado Health Sciences Center, Denver, Colorado, USA
* To whom correspondence should be addressed. E-mail: vivek.balasubramaniam{at}uchsc.edu.
Platelet derived growth factor (PDGF) is a potent smooth muscle cell mitogen that may contribute to smooth muscle hyperplasia during the development of chronic pulmonary hypertension (PH). We studied changes in PDGF 
- and 
-receptor and ligand expression in lambs with chronic intrauterine PH induced by partial ligation of the ductus arteriosus (DA) at gestational age 124-128 days (term = 147 days). Western blot analysis performed on whole lung homogenates from PH animals after 8 days of DA ligation showed a 2-fold increase in PDGF - and -receptor proteins in comparison with age-matched controls (p<0.05). Lung PDGF-A and -B mRNA expression did not differ between PH and control animals. We treated PH animals with NX1975, an aptamer that selectively inhibits PDGF-B, by infusion into the left pulmonary artery for 7 days after DA ligation. NX1975 reduced wall thickness of small pulmonary arteries by 47% (p<0.05) and right ventricular hypertrophy (RVH) by 66% (p<0.02). Lung PDGF - and -receptor expression is increased in perinatal PH, and NX1975 reduces the increase in wall thickness of small pulmonary arteries and RVH in this model. We speculate that PDGF signaling contributes to structural vascular remodeling in perinatal PH, and that selective PDGF inhibition may provide a novel therapeutic strategy for the treatment of chronic PH.
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