The initial lesion of infective endocarditis is thought to be a fibrin-platelet meshwork on an injured cardiac valve - nonbacterial thrombotic endocarditis (NBTE). This lesion is susceptible to colonization by circulating micro-organisms, thereby initiating infective endocarditis (IE). NBTE and subsequent IE do not occur in the ascending aorta. We hypothesize that this disease specificity may in part result from regional variations between the constituent cells of the aorta and valve in their interactions with the hemostatic system. We propose to investigate isolated porcine cell culture systems from four sites: 1) ascending aortic endothelium; 2) ascending aortic subendothelium (smooth muscle cells); 3) aortic valvular endothelium; and 4) aortic valvular subendothelium. We will assess potential differences between these cells in: 1) protein synthesis and expression of cell surface proteins; 2) interactions with platelets and coagulation proteins; 3) responses to platelet and cellular-derived mitogens. The proposed experiments aim to define cellular attributes that could explain how the cardiac valve allows the development of NBTE. The pig is a relevant animal to use in these studies because swine may naturally develop an IE syndrome which clinically resembles human IE.
