Chlamydia pneumoniae is a common human respiratory pathogen. In recent years the scope of C. pneumoniae in human diseases has been extended to the cardiovascular diseases. The studies on seroepidemiology, detection of the organism, and animal models have provided a strong evidence indicating that C. pneumoniae and hyperlipidemia are co-risk factor of atherosclerosis. Because coronary heart disease is a leading cause of death in this country and worldwide, the overall goal of this proposal is to investigate the immunopathogenic mechanisms by which C. pneumoniae promotes the development of vascular disease and to develop the secondary preventive measures for C. pneumoniae-associated atherosclerosis. This research proposal will exploit the recent findings from our studies on the mouse models of C. pneumoniae and atherosclerosis and cell cultures on C. pneumoniae infection using arterial wall cells.
The specific aims are to 1) test the hypothesis that the tropism of C. pneumoniae is dependent on previous activation of the endothelium and expression of adhesion molecules, which facilitates C. pneumoniae homing to and establishing persistent infection at the lesion site to accelerate atherosclerosis; 2) analyze gene expression in foam cell macrophages induced by C. pneumoniae infection by the microarray technique; 3) determine whether infection of hyperlipidemic mice with C. pneumoniae increases expression of Egr-1 responsive genes in the artery wall and whether infection accelerates development of atherosclerotic lesions in Egr-1 knockout mice; and 4) evaluate the ligand-receptor based therapy for prevention of C. pneumoniae-associated atherosclerosis in mice by administering food or water supplemented with mannose 6-phosphate/mannan and retinoic acid. The proposed studies should contribute to the understanding of the disease process and development of better eradication or preventive measures for C. pneumoniae infection and reduction of atherosclerosis and coronary heart disease.
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