Concepts concerning those factors which regulate low density lipoprotein (LDL) concentration composition and metabolism are particularly complex since this lipoprotein class contains at least two major subclasses. LDL heterogeneity or poly-dispersed LDL is of considerable interest because small more dense LDL have been associated with increased atherosclerosis and hyperthyroidism in human subjects. Utilizing a monkey model, the cebus monkey, for which we can isolate two low density lipoproteins, the influence of dietary fat saturation on LDL subclass concentration and composition will be determined. In vivo studies of the catabolism of these LDL subclasses as well as investigation of the metabolism of very low density lipoproteins as a possible precursor of these LDL subclasses will be undertaken. An in vitro liver perfusion system will be utilized to assess direct hepatic formation of LDL subclasses. In vitro studies of cellular binding, uptake and internalization of these LDL subclasses by specific cell types will also be investigated. LDL subclass concentration and composition will be correlated with the degree of atherosclerosis in the cebus monkey.
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| Cladaras, C; Hadzopoulou-Cladaras, M; Avila, R et al. (1986) Complementary DNA derived structure of the amino-terminal domain of human apolipoprotein B and size of its messenger RNA transcript. Biochemistry 25:5351-7 |
