IngentaConnect Apoptogenic Signal Transduction in Arteriosclerosis-Associated Ce...

Abstract:

Atherosclerosis is the most common cause of death in the Western population. Apoptosis has now been recognized as a major event in a number of common and threatening vascular diseases, including in the pathophysiology of atherosclerosis. Consistent with an increasing body of evidence from both, animal models and human specimens, modified low-density lipoprotein-induced apoptosis of vessel wall cells contributes to the development and progression of this disease. Because apoptosis is a highly regulated process and represents the predominant mechanism of cell death in atherosclerosis, its investigation is receiving increasing attention to clarify the underlying molecular mechanisms which will help to design novel specific therapeutic strategies to reduce disease progression. However, since the major cell types involved are blood cells like macrophages (MΦ) and lymphocytes, but also endothelial and smooth muscle cells (Fig. 1), the significance of apoptosis and its relevance in atherosclerosis is likely to be associated with the cell type affected. In this context biochemical, immunocytochemical, functional genomics and genetic analyses provide an increasingly detailed picture of the intracellular signaling pathways being involved in each cell type. For example, extrinsic or intrinsic deathsignaling pathways appear to be activated in blood cells or cells in atherosclerotic lesions and to mediate vascular apoptosis during atherogenesis. We aim to provide a timely overview of apoptogenic signaling pathways in different cell types of the vessel wall, to discuss the relevance of apoptosis in the various cell types and links to inflammation, but also to summarize emerging therapeutic pro-/anti-apoptotic options.

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Apoptogenic Signal Transduction in Arteriosclerosis-Associated Cells -Opportunities for Future Therapy?