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The FASEB Journal • Research Communication Low density lipoprotein misfolding and amyloidogenesis

By Tiziana Parasassi, Marco De Spirito, Giampiero Mei, Roberto Brunelli, Giulia Greco, Laura Lenzi, Eleonora Nicolai, Massimiliano Papi, Silvio C. E. Tosatto and Fulvio Ursini


ABSTRACT In early atherogenesis, subendothelial retention of lipidic droplets is associated with an inflammatory response-to-injury, culminating in the formation of foam cells and plaque. Low density lipoprotein (LDL) is the main constituent of subendothelial lipidic droplets. The process is believed to occur following LDL modification. Searching for a modified LDL in plasma, electronegative LDL [LDL(�)] was identified and found to be associated with major risk biomarkers. The apoprotein in LDL(�) is misfolded, and we show here that this modification primes the aggregation of native LDL, conforming to the typical pattern of protein amyloidogenesis. After a lag phase, whose length depends on LDL(�) concentration, light scattering and atomic force microscopy reveal earl

Year: 2013
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