The objective of this study is to determine the mechanisms of collagen deposition in the evolution and progression of human atherosclerotic lesions. The involvement of the following connective tissue collagens will be immunohistologically determined by procedures devised in our laboratory. These include: interestial collagen types I, II and III; basement membrane collagen comprised of Alpha 1(IV)- an Alpha 2(IV)-chains; pericellular collagens containing Alpha 1(V)-, Alpha 2(V)- and Alpha 3(V) chains; high molecular weight aggregates of type VI collagen. Monoclonal antibodies to these collagens have been produced by the hybridoma technique utilizing mouse myeloma cells (Ag 8.653). Characterization of the antibodies was done for immunoglobulin class, specificity and reactivity by ELISA and immunohistological techniques. The antibody producing hybridomas will be maintained, expanded and used for immunofluorescence and immunoelectronmicroscopic studies of coronary arteries and the aorta of individuals of both sexes, of black and white races and of various ages. The chief parameters to be evaluated in this context are the distribution and disposition of the genetically-distinct types of collagen throughout the vessel wall. Consequently, the antibodies will be utilized to determine the distribution of the different collagens in the matrix immediately adjacent to the proliferated cells and determine the relationship between cells and matrix. Specifically, these studies will provide new data about the intracellular, pericellular and interstitial events during the neosynthesis and deposition of the different collagen types. Moreover, specific changes in the matrix of fatty streaks may reveal the pathogenesis for their transition into the obstructive and largely irreversible fibroatheromatous plaques, as well as determine the collagenous markers involved in the progression of fatty streaks to fibroatheromatous plaques.
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