Plaque rupture and plaque erosion are distinct forms of plaque disruption in relation to their morphology association with risk factors, and sex predisposition. Base don recent morphologic studies from our laboratory, we hypothesize that increased cholesterol deposition in plaques that rupture is derived from RBC membranes from recurrent hemorrhage of ruptured vasa vasorum. This in turn leads to a larger necrotic core size and higher macrophage recruitment, features of vulnerable plaques. In contrast, plaque erosion occurs in plaques that have a rich smooth muscle cell base within a proteoglycan matrix. The higher proteoglycan content correlates with the presence of TGF-beta. We postulate that although estrogen inhibits the formation of large lipid- rich plaques, it does not prevent plaque erosion in the presence of TGF- beta.
The specific aims of the proposal are (a) to establish the relationship between vasorum and plaque hemorrhage; (b) to establish the association between plaque hemorrhage and necrotic core, and nature of cholesterol within the plaque; (c) to establish the association between plaque hemorrhage and activation of macrophages, expression of MMPs, plasminogen activators, and type of collagen deposition; and (d) to establish the association of plaque erosion with the estrus cycle in women less than 50 years of age, the extent and cells producing TGF-beta and PAI-1, and the identification of collagen proteoglycan matrix. Project 1 will work closely with Project 2 and will be responsible for providing the specimens for molecular analysis and immunohistochemical staining for the study of apoptosis. In addition, analysis of plaque morphology in the animal model proposed in Project 4 will be carried out in project 1.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL061799-02
Application #
6078049
Study Section
Special Emphasis Panel (ZHL1-CSR-B (S1))
Project Start
1998-09-30
Project End
2002-09-29
Budget Start
1999-09-30
Budget End
2000-09-29
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
American Registry of Pathology, Inc.
Department
Type
DUNS #
114400633
City
Washington
State
DC
Country
United States
Zip Code
20306
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Kolodgie, Frank D; Burke, Allen P; Wight, Thomas N et al. (2004) The accumulation of specific types of proteoglycans in eroded plaques: a role in coronary thrombosis in the absence of rupture. Curr Opin Lipidol 15:575-82
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Burke, Allen P; Kolodgie, Frank D; Zieske, Arthur et al. (2004) Morphologic findings of coronary atherosclerotic plaques in diabetics: a postmortem study. Arterioscler Thromb Vasc Biol 24:1266-71

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