New insights into the pathogenesis of atherosclerosis as revealed by PDAY. Pathobiological Determinants of Atherosclerosis in Youth

Abstract

In this progress report the major pathological results gained from the research program called The Pathological Determinants of Atherosclerosis in Youth (PDAY) are summarized. These results are made possible because of the many unique features of this multicenter study, which are also summarized. The following main accomplishments utilize special quantitative techniques to study cellular, chemical and molecular (genetic) features of the developing plaques in young people. These include for the first time: The greater incidence of early progressive lesions in selective apo E phenotypes. The greater incidence of progressive lesions 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 thoracic aortic samples, where lesions progress slowly, than in the abdominal aortic core samples, where lesions are much more likely to become severe. A strong correlation between the mast cell population and the concentration of biogenic amines in the lesions. The location of Lp(a) specific antigens in these developing lesions as compared to apo B. The accumulation 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 progression of the plaque is most frequent. Preliminary ultrastructural evidence of intimal platelet and leukocyte adherence and entrance into the intima of the thoracic aorta, where there is likely to be lack of progression of lesions. A review of the recently published biochemical evidence of the correlation of increased lesion cholesterol and collagen content in the abdominal aorta. The continuing studies and their implications are also summarized.