Hormones and growth factors influence cell proliferation in vivo and in vitro. Experimental evidence supports the hypothesis that pituitary-related and platelet-derived growth factors significantly affect vascular smooth muscle cell (SMC) proliferaion. This growth factor cell interaction may determine the extent or rate of fibromusculoelastic plaque formation in atherogenesis. The work described in this proposal will be directed toward identifying which hormones and growth factors result in SMC proliferation in vitro and, more specifically, how the interaction of growth factors from platelet and pituitary controls SMC proliferation. In the long term, such work will clarify the endocrine influences on atherogenesis, will permit the identification of endocrine risk factors, and may result in new approaches to preventive therapy. To accomplish the proposed goals, a serum-free, hormone-supplemental growth medium for rat aortic SMC will be formulated. Similarly, a serum-free medium for the RPM cell (an eternal line of rat bone marrow-derived megakaryoblasts) will be formulated. Thus, the hormonal requirements for growth of both these cell types will be determined. A bovine pituitary-derived mitogen for the RPM cell (not FGF) will be characterized and purified. A SMC mitogen secreted by the RPM cell (PDGF-like), apparently under the influence of the pituitary-derived RPM mitogen, will also be purified. The relationship of the pituitary-derived RPM mitogen to the RPM-derived SMC mitogen will be studied. Finally, the requirement for PDGF and the somatomedins to reconstitute the ability of serum from hypophysectomized rats to support rat SMC proliferation in vitro will be studied. Thus, a platelet-pituitary axis in atherogenesis will be recognized.
