REMODELING OF HDL BY PHOSPHOLIPID TRANSFER PROTEIN - DEMONSTRATION OFPARTICLE FUSION BY H-1-NMR SPECTROSCOPY

There is evidence that phospholipid transfer protein (PLTP) can increa se reverse cholesterol transport by inducing favorable subclass distri bution in the high density Lipoprotein (HDL) fraction. This includes g eneration of initial cholesterol acceptor particles, pre beta-HDL, and of enlarged particles that are rapidly cleared from the circulation. However, partly because of methodological difficulties, the mechanisms behind the PLTP-mediated interconversion of HDL particles are not ful ly understood. In this communication, we describe the use of a novel m ethodology, based on H-1 NMR spectroscopy, to study the PLTP-induced s ize changes in the HDL particles. In accordance with native gradient g el electrophoresis, the 1H MMR data revealed a gradual production of e nlarged HDL particles in the HDL3+PLTP mixtures. In addition, accordin g to a physical model for lipoprotein particles, relating the frequenc y shifts observable with NMR to the size of the Lipoprotein particles, the NMR data demonstrated that PLTP-mediated HDL remodeling involves fusion of the HDL particles. (C) 1998 Academic Press.