Heart attacks and strokes currently kill more people every year than cancer and HIV combined. These cardiovascular diseases are caused by atherosclerosis ‐ the formation of so‐called “plaques” in blood vessels. Interestingly, an enzyme called “Fibroblast Activation Protein (FAP)” contributes to arthritis and inflammatory liver disease; both of which are governed by similar inflammatory mechanisms as atherosclerosis. However the role of FAP in atherosclerosis had never been investigated. The studies presented in this thesis find that FAP is “switched‐on” by inflammation in potentially life‐threatening atherosclerotic plaques. We also found evidence that FAP contributes to plaque destabilization; the main cause of heart attack and stroke. When plaques rupture open, blood clots form, which block the vital flow of oxygen in a dangerous process known as “atherothrombosis.” Our research found that FAP contributes to atherothrombosis in patients who suffered a heart attack. These findings may motivate both the development of anti‐FAP drugs, and also diagnostic measurements of FAP for heart attack and stroke prevention.