A hallmark of psoriasis is a highly proliferated and fenescrated micovascular network. The factors that regulate blood vessel proliferation in this disease are unknown. This proposal will determine the role of cyclic nucleotides and proto-oncogenes in cell replication and differentiation of both normal and psoriatic microvascular skin endothelial cells. Microvascular endothelial cells will be isolated from three types of psoriasis and a comprehensive library of these cells will be established a several growth passages. The responsiveness of the psoriatic cell to vasoactive agents that produce vessel changes in vivo (vasoactive amines, prostaglandins, neuropeptides) will be determined in vitro both biochemically and morphologically by measuring changes in intracellular levels of cyclic AMP and cyclic GMP an by endothelial cell contraction and gap formation in cell monolayers. The fine structure of the cells (cytoplasmic filaments, cell membranes, Weibel-Palade bodies) will be characterized by electron microscopy. Angiogenesis will be measured in cell monolayers by induction of new vessels by collagen gels and the modulation of 4 proto-oncogenes (c-ras, c- myc, c-sis, and c-fos) will be determined by Northern blot analysis. The fine structure of the normal and psoriatic vessels at each stage of differentation will be analyzed by electron microscopy. These studies will provide basic information on the biochemistry and ultrastructure of both the normal and psoriatic skin microvascular endothelial cell and will determine if the abnormalities in the growth of blood vessels in psoriasis can be traced to genetic defects in the regulation of cyclic nucleotides essential for cell growth and function.
