The overall aim of this phased investigator-initiated, multi-center, cooperative study, is to elucidate many of the complex questions concerning the pathogenesis of antherosclerosis. Among the major questions being addressed are: 1) Do all or some fatty streaks progress to fibrous plaques and which are the transitional lesions? 2) What are the morphometric and biochemical lesion changes indicated by progression? 3) What are the frequency and features of insudative and proliferative lesions which may portend progressive disease? 4) What are the qualitative and quantitative effects of risk factors on lesions? 5) What sex differences in lesions account for the paradoxical excess of fatty streaks in young females, even though males develop advanced and clinically manifest disease earlier? This part of the study is concerned with the role of calcium as it relates to some of the above questions. Our working hypothesis is that calcium deposited in the arterial wall enhances the development and progression of the atheroma and may play a role in the transformation of fatty streaks and proliferative lesions into fibrous plaques. The parameters which will be compared with the calcium concentrations are quantitative morphometric measurements of the various lesion types, the amounts of the various lipids, the cellularity of the lesion and its collagen content. In this laboratory we will, in addition to calcium, measure cell proliferation, as indicated by DNA concentration and synthesis, and collagen (the morphometric measurements and the lipid classes will be studied by other Centers). The multi-element nature of the procedure to be used in quantitating calcium, X-ray fluorescence spectroscopy (XRF), will allow us to obtain information regarding trace elements which have been linked to atherogenesis without any additional work or expense.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Unknown (R10)
Project #
5R10HL033765-02
Application #
3433073
Study Section
(SRC)
Project Start
1985-06-01
Project End
1990-07-31
Budget Start
1986-06-01
Budget End
1987-02-28
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Albany Medical College
Department
Type
Schools of Medicine
DUNS #
City
Albany
State
NY
Country
United States
Zip Code
12208
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
McGill Jr, H C; McMahan, C A; Zieske, A W et al. (2000) Associations of coronary heart disease risk factors with the intermediate lesion of atherosclerosis in youth. The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. Arterioscler Thromb Vasc Biol 20:1998-2004
McGill Jr, H C; McMahan, C A; Herderick, E E et al. (2000) Effects of coronary heart disease risk factors on atherosclerosis of selected regions of the aorta and right coronary artery. PDAY Research Group. Pathobiological Determinants of Atherosclerosis in Youth. Arterioscler Thromb Vasc Biol 20:836-45
McGill Jr, H C; McMahan, C A; Herderick, E E et al. (2000) Origin of atherosclerosis in childhood and adolescence. Am J Clin Nutr 72:1307S-1315S
McGill Jr, H C; McMahan, C A; Zieske, A W et al. (2000) Association of Coronary Heart Disease Risk Factors with microscopic qualities of coronary atherosclerosis in youth. Circulation 102:374-9

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