Atherothrombotic vascular disease is often triggered by a distinct type of atherosclerotic lesion that displays features of impaired inflammation resolution, notably a necrotic core and thinning of a protective fibrous cap that overlies the core. A key cause of plaque necrosis is defective clearance of apoptotic cells, or efferocytosis, by lesional macrophages, but the mechanisms underlying defective efferocytosis and its possible links to impaired resolution in atherosclerosis are incompletely understood. Here, we provide evidence that proteolytic cleavage of the macrophage efferocytosis receptor c-Mer tyrosine kinase (MerTK) reduces efferocytosis and promotes plaque necrosis and defective resolution. In human carotid plaques, MerTK cleavage correlated with plaque necrosis and the presence of ischemic symptoms. Moreover, in fat-fed LDL receptor–deficient (
Bishuang Cai, Edward B. Thorp, Amanda C. Doran, Brian E. Sansbury, Mat J.A.P. Daemen, Bernhard Dorweiler, Matthew Spite, Gabrielle Fredman, Ira Tabas
Suppression of MerTK cleavage improves features of resolution in plaques and increases aortic content of specialized proresolving mediators.