Von Willebrand factor medates distinct mechanisms of vegetation formation in streptococcus mutans-induced endocarditis: comparisons between damage-induced and inflammation-induced mouse models.

Infective endocarditis (IE) is a severe cardiovascular disease characterized by the formation of vegetations on heart valves. This study investigates the role of von Willebrand Factor (VWF) in the pathogenesis of Streptococcus mutans-induced endocarditis using two distinct mouse models: damage-induced and inflammation-induced endocarditis. We employed histological analysis, immunofluorescence, scanning electron microscopy, and molecular techniques to elucidate the mechanisms of vegetation formation and the contribution of VWF in each model. Our results demonstrate that VWF is critical for vegetation formation in S. mutans-induced IE, with more pronounced effects in damage-induced models. VWF deficiency reduces valve colonization, and vegetation size, while supplementation restores these phenotypes. Mechanistically, VWF might upregulates IL-17A/ICAM-1 signaling to amplify inflammation and collagen deposition, which was validated by genetic knockout and antibody blockade. Furthermore, our study provides novel insights into the interplay between VWF and inflammatory responses during endocarditis progression, opening new avenues for understanding the complex pathophysiology of this life-threatening condition.