Toll-Like Receptor-4 and Lipoprotein Accumulation in Macrophages

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• 作者：Yury I. Miller ; Soo-Ho Choi ; Longhou Fang ; Richard Harkewicz
• 刊名：Trends in Cardiovascular Medicine
• 出版年：2009
• 出版时间：October 2009
• 年：2009
• 卷：19
• 期：7
• 页码：227-232
• 全文大小：391 K

文摘

Excessive lipid accumulation in macrophages, also known as foam cell formation, is a key process during the development of atherosclerosis, leading to vascular inflammation and plaque growth. Recent studies have identified a new mechanism of macrophage lipid accumulation in which minimally oxidized low-density lipoprotein (mmLDL) and its active components, polyoxygenated cholesteryl ester hydroperoxides, are involved in endogenous activation of toll-like receptor-4 (TLR4), leading to recruitment of spleen tyrosine kinase (Syk), robust cytoskeletal rearrangements and macropinocytosis. In hyperlipidemic environments, mmLDL-induced, TLR4- and Syk-dependent macropinocytosis leads to substantial lipid accumulation in macrophages and monocytes, which may constitute an important mechanism of foam cell formation in atherosclerosis. A novel hypercholesterolemic zebrafish model of early stages of atherosclerosis was used to demonstrate that the TLR4 deficiency significantly reduces the in vivo rate of macrophage lipid accumulation in vascular lesions.