NEW INSIGHTS INTO THE PATHOGENESIS OF ATHEROSCLEROSIS AS REVEALED BY PDAY

In this progress report the major pathological results gained from the research program called The Pathological Determinants of Atherosclero sis in Youth (PDAY) are summarized. These results are made possible be cause of the many unique features of this multicenter study, which are also summarized. The following main accomplishments utilize special q uantitative techniques to study cellular, chemical and molecular (gene tic) features of the developing plaques in young people. These include for the first time: The greater incidence of early progressive lesion s in selective apo E phenotypes The greater incidence of progressive l esions in black youth with an apo B deletion genotype The much higher concentration of epitopes of oxidized LDL in smokers than non-smokers More prevalent macrophages and lymphocytes in the standardized thoraci c aortic samples, where lesions progress slowly, than in the abdominal aortic core samples, where lesions are much more likely to become sev ere A strong correlation between the mast cell population and the conc entration of biogenic amines in the lesions The location of Lp(a) spec ific antigens in these developing lesions as compared to apo B The acc umulation of extracellular lipid where progression of lesions is most rapid, with special emphasis on the effects of smoking The correlation of modulation of the intimal smooth muscle cells with the sites where progresion of the plaque is most frequent Preliminary ultrastructural evidence of intimal platelet and leukocyte adherence and entrance int o the intima of the thoracic aorta, where there is likely to be lack o f progression of lesions A review of the recently published biochemica l evidence of the correlation of increased lesion cholesterol and coll agen content in the abdominal aorta The continuing studies and their i mplications are also summarized.