Hypotriglyceridemic Drugs and Lipoprotein Catabolism
In the last DALM Symposium, we described in detail our findings of abnormal lipoprotein systems in human subjects with dyslipoproteinemia, predominantly hypertriglyceridemia (HTG) (1). These studies, recently published (2,3), can be summarized as follows: HTG states are associated with excessive lipid transfer reactions (4). The lipids that are transferred are the hydrophobic cholesteryl ester (CE) and triglyceride (TG) molecules. The reaction thus causes excessive enrichment of VLDL with CE (5,6), while both LDL and HDL lose CE and acquire TG (1,2,7). Since acquired TG in LDL and HDL are hydrolyzed by plasma lipases (8,9), the particles become smaller and denser as compared to the normal lipoproteins. On the basis of these observations; we suggested abnormal metabolism of HTG-lipoproteins (1). For VLDL, we showed that the large and less dense populations, VLDL-I and VLDL-II, contain 50–150% more CE molecules than present in LDL, and pointed out that such particles cannot complete the VLDL → LDL conversion cascade. Hence, in HTG, “remnants” of these VLDL populations must be cleared from the plasma independently of the LDL pathway (1,5). HTG-LDL is CE-poor, TG-rich, small and dense lipoprotein, and the cholesterol content of the LDL decreases with a curvilinear relation to plasma TG levels. Such LDLs, therefore, are expected to be inefficient regulators of cellular metabolic activities that depend on cholesterol influx, e.g., cholesterol synthesis and B,E receptor protein activity. These postulates have been further investigated in our laboratory during the last 3 years, using LDL and cultured human skin fibroblasts.
KeywordsCholesteryl Ester Human Skin Fibroblast Cellular Metabolic Activity Plasma Lipase Inefficient Regulator
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