Serum amyloid A protein generates preβ1 high-density lipoprotein from α-migrating high-density lipoprotein

Serum amyloid A protein (SAA), an acute-phase reactant in reactive amyloidosis, has high affinity for high-density Lipoprotein (HDL). When SAA is added to HDL, SAA displaces apolipoprotein A-I (apoA-I) and phospholipid from the HDL particles. These dissociated components may form pre beta 1-HDL because free apoA-I can associate with phospholipid to become a lipoprotein having pre beta mobility. To determine whether SAA generates pre beta 1-HDL from alpha-migrating HDL, we investigated the effects of recombinant SAA on HDL subfraction concentration using nondenaturing two-dimensional gradient gel electrophoresis. When we added SAA (0.5 mg/mL) to plasma, the pre beta 1-HDL concentration increased by 164% (from 4.7% +/- 1.3% to 12.4% +/- 3.2% of apoA-I, p < 0.005), The increase in pre beta 1-HDL was proportional to the dose of SAA, When we added SAA to a column of Sepharose beads coupled to the isolated HDL (alpha-migrating HDL), pre beta 1-HDL was dissociated from the column together with the SAA-associated HDL. In summary, we demonstrate that SAA generates pre beta 1-HDL from alpha-migrating HDL. We speculate that SAA-mediated HDL remodeling may take place in inflammation.