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Apoptosis and Efferocytosis in Mouse Models of Atherosclerosis

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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.

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Keywords: APOE; Advanced Atherosclerosis; ER stress; inflammation; macrophage proliferation

Document Type: Research Article

Publication date: December 1, 2007

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  • Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will be devoted to a single timely topic, with series of in-depth reviews, written by leaders in the field, covering a range of current topics on drug targets. These issues will be organized and led by a guest editor who is a recognized expert in the overall topic. As the discovery, identification, characterisation and validation of novel human drug targets for drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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