Degenerative aortic valve disease is the second most common heart disease in adults and predisposes for life-threatening endocarditis. Inflammation is a prominent feature of disease progression. Platelets drive the thrombo-inflammatory response. At sites of valve injury, platelets release inflammatory and antimicrobial chemokines that influence the inflammatory and immune defence system of affected valves. We will elaborate the role of platelet-derived chemokines in the pathophysiology of inflammatory aortic valve disease using a variety of genetic mouse strains, infection models, and – for the first time – in human material to identify novel diagnostic and therapeutic strategies.