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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Unknown (R10)
Project #
5R10HL033733-03
Application #
3433006
Study Section
(SRC)
Project Start
1985-06-01
Project End
1990-07-31
Budget Start
1987-03-01
Budget End
1988-02-29
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
Schools of Medicine
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
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
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

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