Apoptosis and efferocytosis in mouse models of atherosclerosis.
Throughout the process of atherosclerosis, lesional macrophages, smooth muscle cells, and possibly endothelial cells undergo programmed cell death, or apoptosis. Under normal physiologic conditions, apoptotic cells are rapidly cleared by neighboring phagocytes, a process called efferocytosis, which prevents secondary cellular necrosis and inflammation. If efferocytosis is not efficient, necrosis, inflammation, and tissue damage ensue. Mouse models of atherosclerosis offer the best opportunity to understand the mechanisms and consequences of lesional cell apoptosis and efferocytosis in atherogenesis and plaque progression. Studies in mice to date have suggested that properly coupled macrophage apoptosis and efferocytosis in early atherosclerosis limits lesion size. The results of other mouse studies suggest that macrophage and smooth muscle cell apoptosis and defective efferocytosis in advanced lesions promotes plaque necrosis. Future insight into these critically important processes will require additional insight into the molecular and cellular mechanisms that lead to lesional cell apoptosis and efferocytosis as well as new mouse models of plaque disruption and thrombosis. Advances in these areas offer great hope for eventual translation into innovative therapeutic strategies to combat atherothrombotic vascular disease.
Tabas
Ira
I
Departments of Medicine, Pathology & Cell Biology, and Physiology & Cellular Biophysics (I.T.), Columbia University, New York, NY 10032, USA. iat1@columbia.edu
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D050197:Atherosclerosis / Q000276:immunology* / Q000503:physiopathology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000276:immunology / Q000473:pathology; D009336:Necrosis / Q000276:immunology / Q000473:pathology; D010586:Phagocytes / Q000276:immunology / Q000473:pathology; D013927:Thrombosis / Q000473:pathology