Vascular remodeling observed in the fetal bovine hypoxic pulmonary hypertension model is associated with a stable alteration in the smooth muscle cell phenotype. Previous studies from this laboratory have shown that this modulation is characterized by increased collagen and elastin production. Additional studies have shown that the steady-state expression of both the collagen and elastin mRNA transcripts is increased, consistent with regulation at the transcriptional level. Collagen and elastin synthesis or mRNA expression should now prove useful markers of this altered phenotype in studies aimed at identifying earlier participants in the mechanism(s) coupling hypertension with vascular remodeling. Growth factors have a profound effect on cell structure and differentiation and, therefore, are likely to participate relatively early in vascular remodeling. They are capable of stimulating cell growth, inducing cellular differentiation and causing cellular modification of the extracellular matrix. However, the actual role of growth factors in altering the hypertensive pulmonary artery smooth muscle cell has yet to be carefully studied. The long-term goal of this work is to study how growth factors are involved in smooth muscle cell differentiation and gene expression using a model that may allow new insights into the pathogenesis of a human disease for which no satisfactory therapy currently exists. Characterizing the in vivo temporal and topographical changes of growth factor mRNA expression in hypertensive pulmonary arteries is possible using established techniques in molecular biology. Correlating changes in growth factor mRNA expression and collagen and elastin mRNA expression (previously characterized markers of this phenotypic alteration) will tentatively establish the relevant mitogen(s) or differentiation factors as an early mediator in the mechanism coupling hypertension to vascular remodeling. Careful in vitro studies can more fully characterize the role of those growth factors in the modulation of smooth muscle cell phenotype using collagen and elastin production as a marker.
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