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CD47-Blocking Antibodies and Atherosclerosis

http://basictranslational.onlinejacc.org/content/1/5/413

In this paper (2), CD47 was found to be increased in the atherosclerotic regions of human coronary and carotid arteries. Of note, the increase in CD47 was localized to the necrotic core of the plaques and was up-regulated to a greater extent in people with a history of stroke or transient ischemic attack, compared with samples from patients with stable asymptomatic carotid lesions. On the basis of the intriguing human and in vitro data, the authors studied the role of CD47 in apolipoprotein E-/- mice treated with angiotensin II infusion—a small animal model prone to the development of atherosclerosis. When these animals were treated with inhibitory antibodies directed against CD47, Kojima et al. (2) found a marked reduction in atherosclerosis compared with those treated with immunoglobulin G control. In other models of chronic atherosclerosis, and in models more reflective of the clinical disease state observed in humans, the authors found that anti-CD47 antibodies had similar effects. The authors also found that there was a marked decrease in residual apoptotic bodies in the atherosclerotic plaque of animals treated with anti-CD47 antibodies, consistent with impaired efferocytosis in atherosclerosis. Additionally, colocalization studies and electron microscopy studies demonstrated that the number of free apoptotic bodies (i.e., not associated with an intraplaque macrophage) was decreased after anti-CD47 antibody treatment, thereby implicating failed efferocytosis in the pathogenesis of CD47-mediated atherosclerosis. Furthermore, the atherosclerotic lesions in the animals treated with anti-CD47 antibodies had smaller necrotic cores and less apoptotic debris.