Prostaglandin E1 and peptide growth factors stimulate neonatal pulmonary artery smooth muscle cell proliferation in a synergistic manner. † 1544

Abnormal pulmonary artery smooth muscle cell (PASMC) proliferation is involved in the pathogenesis of pulmonary vascular remodeling. Several peptide growth factors stimulate smooth muscle proliferation, while some vasodilators(e.g. nitric oxide) have an inhibitory effect. The action of prostaglandins is less clearly defined, and the effect has been reported to be different for adult aortic and pulmonary artery smooth muscle cells. We evaluated the effects of basic fibroblast growth factor (bFGF, a competence factor), insulin-like growth factor-1 (IGF-1, a progression factor), and prostaglandin E1 (PGE1) on neonatal PASMC proliferation. We used PASMC isolated from the main pulmonary artery of newborn piglets and assessed cellular proliferation by chemosensitivity assays after 24 hours of exposure to different combinations of these factors (5ng/ml bFGF, 20ng/ml IGF-1, 1mg/ml PGE1) in serum free media. As expected. bFGF and IGF-1 stimulated PASMC proliferation. PGE1 also increased PASMC proliferation and its action was synergistic with both growth factors (p<0.05 by ANOVA). To further evaluate the mechanism involved in this action, we tested the hypothesis that PGE1 stimulates the local production of IGF-1 in PASMC (as happens in osteoblasts). The experiment was repeated with the addition of angiopeptin (a somatostatin analogue that inhibits the synthesis of IGF-1). The effect of PGE1 on PASMC proliferation was not changed by angiopeptin, suggesting that PGE1 action is not due to an increased production of IGF-1 by PASMC. These results, if applicable to in vivo conditions, suggest that the administration of PGE1 to newborns with congenital heart defects may contribute to the development of abnormal pulmonary vascular remodeling and chronic pulmonary hypertension.Table

Table 1

PASMC proliferation (% increase at 24 h) (mean±SD)