Modulation of bacterial adherence in infective endocarditis: impact of different conduit tissues used in right ventricular outflow tract valve replacement and bacterial surface molecules under shear stress.

Infective endocarditis (IE) is defined as an infection of the endocardial surface of the heart, which may include one or more heart valves, and is lethal if not aggressively treated. IE can have numerous causes, but is a major clinical problem in patients after transcatheter or surgical valve replacement. Treatment of IE is challenged by the high propensity of bacteria, in particular Staphylococcus aureus, to induce inflammatory and procoagulant responses (e.g. via endothelial cells and platelet activation) allowing them to concentrate in cardiac vegetations where they escape elimination by the host. Novel therapeutic revalvulation strategies aim to minimize risk factors and increase biocompatibility. In this proposal, we want to understand how the underlying valve conduit tissues modify the onset of IE with respect to bacterial adhesion and subsequent inflammation. The emphasis will be on flow-controlled processes, which exert mechanical forces on the tissue surface- and endothelial cells-bacterial cross talk similar to those found in the human situation. A better knowledge of this mechanisms aim a therapeutic application to reduce the IE risk associated with revalvulation.