PROTEIN-COMPOSITION DETERMINES THE ANTI-ATHEROGENIC PROPERTIES OF HDLIN TRANSGENIC MICE

HIGH-DENSITY lipoprotein (HDL) contains two major proteins, apolipopro tein A-I (apoA-I) and apolipoprotein A-II (apoA-II), comprising about 70% and 20% of the total HDL protein mass, respectively. HDL exists in human plasma in two main forms, one containing apoA-I with apoA-II (A I/AII-HDL) and another containing apoA-I without apoA-II (AI-HDL). A s trong inverse relationship exists between total plasma HDL concentrati on and atherosclerosis, but the results of studies examining the relat ionship between AI-HDL and AI/AII-HDL and atherosclerosis have been co nflicting1-9. To determine whether these two HDL populations have diff erent effects on atherogenesis, human apoA-I (AI) and human apoA-I and apoA-II (AI/AII) transgenic mice were produced in an atherosclerosis- susceptible strain10-12. Following an atherogenic diet, despite simila r total cholesterol and HDL cholesterol concentrations, the area of at herogenic lesions in the AI/AII mice was 15-fold greater than in the A I animals. These studies show that the protein composition of HDL sign ificantly affects its role in atherogenesis and that AI-HDL is more an ti-atherogenic than AI/AII-HDL.