| Research Abstract |
1.We investigated the effects of subclasses of LpA-I [high density lipoprotein (HDL) containing only apoA-I] on cholesterol esterification in plasma and net cholestrol efflux from foam cells. LpA-I was composed of particles of three different sizes : large (Lg-LpA-I), medium (Md-LpA-I) and small (Sm-LpA-I). Plasma concentrations of LpA-I were positively correlated only with the level of Lg-LpA-I.Plasma concentrations of Lg-LpA-I were inversely correlated with the rate of cholesterol esterification in plasma and VLDL and LDL-depleted plasma (FERplasma and FER_<HDL>). When macrophage foam cells were incubated with Md-and Sm-LpA-I,cellular cholesterol mass was reduced by approximately 70%. In contrast, the cellular cholesterol-reducing capacity of Lg-LpA-I was negligible. Lg-LpA-I inhibited net cholesterol removal from foam cells that was mediated by Md-and Sm-LpA-I and cholesteryl ester production with these particles. These results suggest that Md-and Sm-LpA-I may actively participate i
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n cellular cholesterol removal and cholesterol esterification in plasma and HDL,while Lg-LpA-I may regulate these functions of Md-and Sm-LpA-I.
2.We examined the correlations between low-density-lipoprotein (LDL) particle size and both FER_<HDL> and plasma lipid levels. FER_<HDL> and plasma triglyceride were negatively, and HDL-cholesterol was positively, correlated with LDL particle size (r=-0.728, -0.598and0.572, p>0.0001). Stepwise multiple regression analysis revealed that FER_<HDL> was most significantly associated with LDL particle size. Since FER_<HDL> is regulated by the plasma consentration of LpA-I (HDL containig apoA-I but not apoA-II), which is the anti-atherogenic fraction of HDL,the present results suggest that the regulation of LDL particle size may be part of the anti-atherogenic nature of LpA-1.
3.Qualitative and quantitative changes of LpA-I in children with low plasma LpA-I were indistinguishable from those in patients with coronary artery disease (CAD) with low plasma LpA-I.All of our data suggest that children with low plasma LpA-I are high risk for CAD. Less
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