Plasma triglyceride determines structure-composition in low and high density lipoproteins.

Because the association of hypertriglyceridemia and premature atherosclerosis is not due to the direct effects of the triglyceride molecule itself, we studied the effects of increased plasma triglyceride-rich lipoproteins on the composition and structure of low density lipoprotein (LDL) and high density lipoprotein (HDL). We found profound changes in the core and surface domains of both lipoproteins with increasing triglyceridemia. Core cholesterol esters were progressively depleted and replaced by triglyceride molecules. Highly significant negative correlations were found between cholesterol ester/protein ratios (r = -0.64 for LDL and -0.58 for HDL (p less than 0.001); positive correlations were found for triglyceride/protein ratios (r = 0.62 for LDL and 0.58 for HDL) and for triglyceride/cholesterol ester ratios (r = 0.70 for LDL and 0.83 for HDL) when these variables were assayed as a function of plasma triglyceride concentrations. With severe hypertriglyceridemia, triglyceride/cholesterol ester ratios of more than 1.0 were consistently observed (normal, less than 0.02). This leads to an underestimation of LDL and HDL levels when cholesterol alone is measured. At the surface, LDL and HDL were depleted of phospholipid and free cholesterol, with a relative enrichment of protein. These changes can be explained on the basis of high levels of plasma triglyceride-rich lipoproteins serving as acceptors for cholesterol esters and other constituents from LDL and HDL. Concomitantly, triglycerides are transferred to LDL and HDL. These transfer processes are likely to be mediated by the activity of lipid transfer proteins present in human plasma.