Biotecnologia

ity, can result in the FCHL phenotype. Although decreased LDL receptor activity is not thought to be the primary defect in human FCHL (1, 2), LDL cholesterol and APOB amounts appear to be influenced by LDL receptor activity (21). In APOC3 transgenic mice, hypertriglyceridemia arises from a delay in clearance of VLDL (7), reflecting an in vivo lipolysis defect (7, 22), which may be caused bydecreased binding of VLDL to endothelial cell proteoglycans, impairing access to LPL (22–24). It is possible that low LDL receptor activity results in increased conversion of accumulating VLDL into IDL and LDL. Other hypertriglyceridemia genes also might produce the FCHL phenotype. For example, deficiency of LPL activity has been found in some FCHL families (6, 25). Although this is not usually becauseof alterations in the LPL gene itself (25), other genes that diminish LPL activity might underlie FCHL in some instances.
REFERENCES AND NOTES ___________________________
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sis 7, 203 (1987). 22. K. Aalto-Setala et al., J. Lipid Res. 37, 1802 (1996). ¨ ¨ 23. Z.-S. Ji, S. Fazio, Y.-L. Lee, R. W. Mahley, J. Biol. Chem. 269, 2764 (1994). 24. N. S. Schacter et al., J. Clin. Invest. 98,846 (1996). 25. W.-S. Yang, D. N. Nevin, R. Peng, J. D. Brunzell, S. S. Deeb, Proc. Natl. Acad. Sci. U.S.A. 92, 4462 (1995); E. Gagne, J. Genest Jr., H. Zhang, L. A. Clarke, M. R. Hayden, Arterioscler. Thromb. 14, 1250 (1994). 26. K. A. Kieft, T. M. A. Bocan, B. R. Krause, J. Lipid Res. 32, 859 (1991). Diluted samples of pooled plasma from groups of five or six mice were analyzed by using...