Small LDL症例における抗動脈硬化作用を有するHDLサブクラスの検討

Abstract

HDL consists of heterogeneous lipoproteins and plays an important role for antiatherogenic function. HDL can be clarified either by its apolipoprotein composition: Lp A-I containing apo A-I but no apo A-II and Lp A-I/A-II containing both apo A-I and apo A-II, or by its particle size:large sized HDL2 and small sized HDL3. Recent studies have indicated that specific HDL subclasses may be responsible for antiatherogenic properties.To confirm antiatherogenic HDL subclasses independendent of HDL cholesterol levels, we investigated the relationship between HDL subclasses and angiographically documented coronary artery disease (CAD) in 125 patients with a predominance of small LDL, which has been recognized as atherogenic state with dyslipidemia of low HDL cholesterol and high triglycerides.Patients with diabetes mellitus or who were taking lipid-lowering drugs were excluded. CAD(+) was defined as ≥50% stenosis in major coronary arteries. Lp A-I particles was quantified as the concentration of apo A-I in these particles by using a differential electroimmunoassay with hydrated agarose gels containing monospecific antibodies against apo A-I and apo A-II.HDL2 were examined by 4∼30% nondenaturing polyacrylamide gradient gel electrophoresis and the percentage of HDL2 protein (%HDL2) of the total HDL protein on densitometric scan area were determined.The CAD(+) group (n=82) had older patients (p=0.02) and higher proportion of male (p=0.01) compared with CAD(-) group (n=43). Although both groups had high levels of triglycerides and low levels of HDL cholesterol and apo A-I, there were no significant differences between the two groups.Analysis of HDL subclasses revealed that Lp A-I levels were significant lower in CAD(+) than in CAD(-) (37.5±11.4mg/dl vs. 54.2±13.4mg/dl, p<0.0001) and %HDL2 were also lower in CAD(+) than in CAD(-) (17%vs. 26%, p=0.08).CAD(+) frequency was lowest in highest quartiles of Lp A-I levels (23%) and it was inversely associated with Lp A-I levels (p<0.001).HDL cholesterol and Lp A-I were not associated with triglycerides, however, %HDL2 exhibited a significant correlation with triglycerides (r=0.56, p=0.046).These findings indicate that Lp A-I and HDL2 levels represent a protective effect of HDL subclasses independent of HDL cholesterol levels in individuals with a predominance of small LDL.We conclude that HDL metabolism producing largesized HDL containing only apo A-I may be important for antiatherogenic function.