The overall objective of our Program Project Grant is to characterize the cellular and molecular events which mediate the intense inflammatory response that occurs rapidly upon reperfusion of the previously ischemic myocardium. This inflammatory response represents a classic reaction to injury and substantial evidence suggests that it may extend cardiac injury. The three projects of this Program Project Grant all are directed at characterizing the cellular and molecular events that control adhesion molecule induction, expression, activation, and adhesion molecule mediated cellular events. Adhesion molecules govern and control leukocyte trafficking, leukocyte secretion and leukocyte mediated injury and the understanding of their metabolism is critical to the understanding of the inflammatory reaction to injury ensuing from reperfusion. Project 1 utilizes a chronic animal model of ischemia and reperfusion in which the cardiac lymph duct can be cannulated to allow access to cardiac extracellular fluid in animals in whom there is no surgical trauma. The role, induction, and activation of adhesion molecules is studied by measurements of leukocyte flux, immuno- cytochemistry, in situ hybridization, and quantitative Northern blotting. Project 2 takes advantage of a newly developed mouse model of ischemia and reperfusion and is designed to study the consequence of genetic deletion of specific adhesion molecules, chemotactic agents and chemotactic receptors. Molecular and cellular consequences of gene deletion are studied. Project 3 deals with the cellular and molecular mechanisms by which individual adhesion molecules control leukocyte trafficking, leukocyte secretion, and leukocyte induced cardiac injury.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
2P01HL042550-06
Application #
2220577
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
1990-05-01
Project End
2000-06-30
Budget Start
1995-07-01
Budget End
1996-06-30
Support Year
6
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
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