Infective endocarditis is an illness that usually afflicts persons who have either had previous damage to their heart or who have congenital heart disease. At times, however, endocarditis occurs In otherwise normal hearts. Endocarditis results from colonization of cardiac tissues by micro-organisms, typically oral streptococci, that gain access to the blood stream and cause brief bacteremias. An important aspect of the pathophysiology of infective endocarditis is the marked propensity of the cardiac valve to bind and allow proliferation of micro-organisms. There Is evidence that this peculiar propensity could be related to the development on the cardiac valve of nonbacterial thrombotic endocarditis (NBTE) following injury; other vascular tissues do not form NBTE. This application will continue our work on the cell biology of the porcine cardiac valve, proposing four specific aims of potential relevance to the understanding of the cellular basis of infective endocarditis: 1) what properties of cardiac valvular cells may affect their interaction with platelets or bacteria; 2) host bacteria interact with platelets; 3) do valve endothelial cells possess unique surface markers; 4) that procoagulant properties are present in cardiac valve cells. The experiments use isolated cell culture systems of porcine vascular endothelial and smooth muscle cells, and compare then to porcine aortic valvular endothelial and subendothelial cells. These comparisons Include binding of bacteria and platelets and coagulation of the coagulation system on cellular monolayers. In addition, bacterial- platelet interactions will be assessed. The ultimate aim is to explore unique attributes of valvular cells that might explain the propensity of that tissue to develop infective endocarditis. Such knowledge could be crucial toward understanding how to intervene to prevent this illness.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL032752-08
Application #
3344220
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1985-04-01
Project End
1993-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
8
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905
Johnson, C M (1993) Adherence events in the pathogenesis of infective endocarditis. Infect Dis Clin North Am 7:21-36
Johnson, C M (1993) Staphylococcus aureus binding to cardiac endothelial cells is partly mediated by a 130 kilodalton glycoprotein. J Lab Clin Med 121:675-82
Johnson, C M; Helgeson, S C (1993) Fibronectin biosynthesis and cell-surface expression by cardiac and non-cardiac endothelial cells. Am J Pathol 142:1401-8
Carson, C W; Hunder, G G; Kaplan, K L et al. (1991) Inducible release of an endothelial cell-specific protein. Am J Pathol 139:199-206
Campbell, K M; Johnson, C M (1990) Identification of Staphylococcus aureus binding proteins on isolated porcine cardiac valve cells. J Lab Clin Med 115:217-23