Abstract
Background: Serum pre beta 1-high density lipoprotein (pre beta 1-HDL) was defined by two-dimensional non-denaturing linear gel electrophoresis and apolipoprotein A-I immuno-blotting. Serum pre beta 1-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.
Methods: We isolated the pre beta 1-HDL using a new native polyacrylamide gel electrophoresis (PAGE) system and lipid pre-staining serum. We established a two-demensional gel electrophoresis system.
Results: We measured the pre beta 1-HDL in Tangier disease patients and subjects with cholesterol ester transfer protein (CETP) mutation. The pre beta 1-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 pre beta 1-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 pre beta 1-HDL particles. We recruited a total of 102 subjects underwent diagnostic coronary angiography and measured their pre beta 1-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 pre beta 1-HDL is independently and negatively associated with the severity of the coronary artery stenosis (Gensini score).
Conclusion: We established a novel and simple method for human serum pre beta 1-HDL quantification. We found that human lower pre beta 1-HDL is an independent predictor for severer coronary artery stenosis.