Coronary artery disease, the primary cause of death in the western world, is induced by an acute cessation of the blood flow due to the formation of an occluded thrombus or blood clotin or nearby an unstable atherosclerotic lesion. Whether or not thrombotic complications will ensue from plaque rupture is strongly dependent on the presence of procoagulant molecules within the plaque. Interference with their activity thus represents a promising approach to influence the initiation and progression of the disease. The general goal of the project is:
- to inhibit expression and activity of procoagulant proteins by delivering specific enzymes and,
- to modulate the activity of transcription factors regulating these proteins.
Modulation will be effected by atherosclerotic plaque-directed adenoviral gene transfer, bone marrow transplantation from corresponding transgenics and administration of therapeutic inhibitors in an advanced mouse model of accelerated atherosclerosis. The effect on the plaque size and morphology as well as on its lipid content and thrombotic nature will be determined. We anticipate that the results will lead to new therapeutic entries for reducing the thrombogenicity of atherosclerotic plaques and thus preventing thrombotic complications.
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