Targeting Activated Platelets and Fibrinolysis Hitting Two Birds with One Stone

Acute thrombotic events, such as myocardial infarction and ischemic stroke, are the leading causes of morbidity and mortality worldwide. Based on the data available in 2010, coronary heart disease alone caused ≈1 of every 6 deaths in the United States.1 Approximately every 34 seconds, an American has a coronary event, and approximately every 1 minute 23 seconds, an American will die from it.1 Thrombolytic drugs are used to dissolve blood clots to avoid downstream tissue damage after occlusive thrombus formation; however, bleeding complications are a major concern. Therefore, the development of a potential thrombolytic agent that does not lead to bleeding represents a highly desirable strategy. In this issue of Circulation Research , Wang et al2 used recombinant technology and successfully generated a novel antibody-targeted fibrinolytic agent that selectively binds to activated platelets and triggers thrombolysis locally without significantly impairing hemostasis. Although the preclinical experiments were performed in murine models, this antibody also cross-reacts with human-activated platelets and both the antibody Fv fragments and urokinase are of human origin, thus this new agent should have great potential in future clinical trials. Article, see p 1083 Acute thrombosis, such as coronary heart disease, usually occurs after rupture of an atherosclerotic plaque.3 Atherosclerosis is a chronic inflammatory process involving a complex interplay of numerous factors including low-density lipoprotein modification, macrophage recruitment, foam cell formation, and immune responses, interacting with normal cellular elements of the arterial wall.4 Recently, studies suggest that platelets are also involved in atherosclerosis. Platelets are now considered immune cells and contribute significantly to inflammation and aspects of the immune response, including leukocyte trafficking, immunoglobulin class-switch, and others,5–8 which may directly or indirectly affect atherosclerosis. In addition, through their surface scavenger receptors, platelets can internalize lipids. Macrophages phagocytose these platelets and develop …