The role of human serum albumin and its structural variants in coronary heart disease

Human serum albumin (HSA) is a major protein component of plasma, and its main function is to transport various endogeneous and exogeneous ligands such as drug, hormone by binding with moderate affinity. HSA is a major fatty acid binding protein and carrier in human serum and HSA binds up to seven fatty acids molecules. Therefore, HSA-fatty acid interactions are important to understand pathogenesis of various lipid metabolism related diseases.;In this study, we used the human EA.hy926 endothelial cell line as the model system to investigate the effects of HSA and its structural variants on cholesterol efflux. The result showed that HSA promoted cholesterol efflux in a dose and time-dependent manner, and more efficient and specific than other cholesterol acceptors such as BSA, or ovalbumin. HSA-mediated efflux occurred via cAMP-independent and relatively temperature insensitive pathway, which was confirmed by using murine RAW 2648 macrophage cells. Also, by using various HSA mutants, we found specific effects of subdomain 2A and 3A mutant proteins on cholesterol efflux. Our study provides evidence for the major role of HSA in cholesterol efflux from peripheral tissues.;We studied the role of HSA, not BSA as opposed to majority of previous studies used, on apo B secretion from cultured human liver HepG2 cells. The results showed that oleic acid was the most effective on apo B secretion and the optimal ratio of HSA:oleic acid affecting apo B secretion was determined to be 1:4. Also, we studied HSA mutants' effects on apo B secretion by using 11 recombinant mutant HSA proteins. Double mutant HSAs showed the most significant effects on apo B secretion. The measurement of the rate of oleic acid uptake rate in the various mutant HSAs also indicated that increased OA binding to mutant HSA resulted in the reduced absorption rate of OA into HepG2 cells.;We investigated statin-mediated modulation of HSA synthesis and secretion by using cultured HepG2 cells. The results showed that simvastatin has the most significant effects on HSA secretion compared to other statins. Simvastatin's effects on HSA secretion was the result of increased rate of new HSA synthesis.