This proposal contains three separate projects from the Medical College of Georgia as part of an investigation initiated multi-center study of pathobiological determinants of atherosclerosis in youth. The long-term objective of this multi-center study is to define more precisely the pathogenesis of human atherosclerosis during the age period of 15-34 years and also to determine if selected risk factors for clinically manifest coronary heart disease in middle age influence the process of atherosclerosis during this age period. The material for the study will be derived from autopsies performed in about 15 centers across the United States of America on disease-free subjects in this age group dying suddenly or from accidents, mostly from vehicular accidents. The material collected will include the aorta and coronary arteries, other tissues and blood and relevant personal data. A multi-pronged approach, utilizing traditional morphological and chemical techniques as well as more sophisticated methodologies, will attempt to answer several specific questions, some of which are outlined below. Do lesions characteristic of later childhood (fatty streaks) evolve into lesions that, in adulthood, are closely associated with arterial occlusion and ischemia (fibrous plaques) If such progression did seem to occur, what are the earliest detectable changes indicative of progression in the fatty streak? Are there differences in regard to the occurrence of microthrombi, collagen composition of the intima, endothelial covering, number, types and qualities of cells populating the intima and trace element and chemical composition? Are there lesions other than fatty streaks that may be precursors of the fibrous plaques? This proposal includes (1) details of collection of specimens from autopsies performed in three hospitals in the Augusta area, (2) a histochemical and histological study of the collagen characteristics of the intima and media and the relationship of the collagen composition to intimal thickness, presence of unesterified cholesterol, neutral fat, smooth muscle proliferation, atheronecrosis and other lesions of intima and media and (3) a scanning electron microscopic study to determine the frequency and characteristics of microthrombi in selected sites of the coronary arterial system and the aorta.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Unknown (R10)
Project #
5R10HL033772-08
Application #
3433091
Study Section
Special Emphasis Panel (SRC)
Project Start
1985-06-01
Project End
1992-07-31
Budget Start
1992-03-01
Budget End
1992-07-31
Support Year
8
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Medical College of Georgia (MCG)
Department
Type
Schools of Medicine
DUNS #
City
Augusta
State
GA
Country
United States
Zip Code
30912
McMahan, C Alex; Gidding, Samuel S; Malcom, Gray T et al. (2007) Comparison of coronary heart disease risk factors in autopsied young adults from the PDAY Study with living young adults from the CARDIA study. Cardiovasc Pathol 16:151-8
Zieske, Arthur W; McMahan, C Alex; McGill Jr, Henry C et al. (2005) Smoking is associated with advanced coronary atherosclerosis in youth. Atherosclerosis 180:87-92
Zieske, Arthur W; Tracy, Russell P; McMahan, C Alex et al. (2005) Elevated serum C-reactive protein levels and advanced atherosclerosis in youth. Arterioscler Thromb Vasc Biol 25:1237-43
Scheer, W Douglas; Boudreau, Donald A; Hixson, James E et al. (2005) ACE insert/delete polymorphism and atherosclerosis. Atherosclerosis 178:241-7
McGill Jr, Henry C; McMahan, C Alex; Herderick, Edward E et al. (2002) Obesity accelerates the progression of coronary atherosclerosis in young men. Circulation 105:2712-8
McGill Jr, H C; McMahan, C A; Zieske, A W et al. (2001) Effects of nonlipid risk factors on atherosclerosis in youth with a favorable lipoprotein profile. Circulation 103:1546-50
Ishikawa, Y; Ishii, T; Akasaka, Y et al. (2001) Immunolocalization of apolipoproteins in aortic atherosclerosis in American youths and young adults: findings from the PDAY study. Atherosclerosis 158:215-25
Rao, R N; Fallman, P M; Falls, D G et al. (1989) A comparative study of PAS-phosphotungstic acid-Diamine Supra Blue FGL and immunological reactions for type I collagen. Histochemistry 91:283-9
Spurlock, B O; Chandler, A B (1987) Adherent platelets and surface microthrombi of the human aorta and left coronary artery: a scanning electron microscopy feasibility study. Scanning Microsc 1:1359-65