Abstract
BackgroundSerum preβ1-high density lipoprotein (preβ1-HDL) was defined by two-dimensional non-denaturing linear gel electrophoresis and apolipoprotein A-I immuno-blotting. Serum preβ1-HDL seems to play an important role in reverse cholesterol transport, a well-known anti-atherosclerosis process. However, there are still debatable questions for its quantification and coronary artery disease (CAD) relevance.MethodsWe isolated the preβ1-HDL using a new native polyacrylamide gel electrophoresis (PAGE) system and lipid pre-staining serum. We established a two-demensional gel electrophoresis system.ResultsWe measured the preβ1-HDL in Tangier disease patients and subjects with cholesterol ester transfer protein (CETP) mutation. The preβ1-HDL is clearly separated from lipid-free apoA-I monomer and cannot be converted into other HDL particles under lecithin-cholesterol acyltransferase (LCAT) inhibition. This preβ1-HDL is a spheroidal particle with the highest apoA-1/cholesterol ratio and highest density (≥1.21 g/ml), as compared with all other HDLs. Importantly, we found that serum from subjects with Tangier disease or with cholesterol ester transfer protein (CETP) mutation have no detectible preβ1-HDL particles. We recruited a total of 102 subjects underwent diagnostic coronary angiography and measured their preβ1-HDL levels. Among them, 56 had no stenosis of coronary artery and 46 were diagnosed as CAD, which was predefined as the presence of a luminal diameter stenosis ≥50 % in at least 1 major coronary artery territory. We found that preβ1-HDL is independently and negatively associated with the severity of the coronary artery stenosis (Gensini score).ConclusionWe established a novel and simple method for human serum preβ1-HDL quantification. We found that human lower preβ1-HDL is an independent predictor for severer coronary artery stenosis.
Highlights
Serum preβ1-high density lipoprotein was defined by two-dimensional non-denaturing linear gel electrophoresis and apolipoprotein A-I immuno-blotting
The same method has been utilized in many clinical studies, including those concerning coronary artery disease (CAD) patients, and the results suggest that an elevated level of preβ1-high density lipoprotein (HDL) is a risk factor for CAD [19,20,21]
We found that neonates had significantly higher HDL (A) than healthy adults and HDL (B) was the predominant HDL particle in healthy adults
Summary
Serum preβ1-high density lipoprotein (preβ1-HDL) was defined by two-dimensional non-denaturing linear gel electrophoresis and apolipoprotein A-I immuno-blotting. Serum preβ1-HDL seems to play an important role in reverse cholesterol transport, a well-known anti-atherosclerosis process. HDL cholesterol concentration in the blood is inversely proportional to coronary artery disease (CAD) risk [1]. This relationship is thought to be mediated by the ability of HDL to transport excess cholesterol from peripheral tissues back to the liver for excretion, a process known as reverse cholesterol transport [2]. Free apoA-I was not seen on the two-dimensional gel in that first paper [16], Francone et al from the same lab clearly showed that lipid-free apoA-I could be separated from preβ1-HDL [17].
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