Expression of serum amyloid A protein in the absence of the acute phase response does not reduce HDL cholesterol or apoA-I levels in human apoA-I transgenic mice

Plasma concentrations of high density lipoprotein (HDL) cholesterol and its major apolipoprotein (apo)A-I are significantly decreased in inflammatory states. Plasma levels of the serum amyloid A (SAA) protein increase markedl y during the acute phase response and are elevated in many chronic inflamma tory states. Because SAA is associated with HDL and has been shown to be ca pable of displacing apoA-I from HDL in vitro, it is believed that expressio n of SAA is the primary cause of the reduced HDL cholesterol and apoA-I in inflammatory states. In order to directly test this hypothesis, we construc ted recombinant adenoviruses expressing the murine SAA and human SAA1 genes (the major acute phase SAA proteins in both species), These recombinant ad enoviruses were injected intravenously into wild-type and human apoA-I tran sgenic mice and the effects of SAA expression on HDL cholesterol and apoA-I were compared with mice injected with a control adenovirus, Plasma levels of SAA were comparable to those seen in the acute phase response in mice an d humans. However, despite high plasma levels of murine or human SAA, no si gnificant changes in HDL cholesterol or apoA-I levels were observed, SAA wa s found associated with HDL but did not specifically alter the cholesterol or human apoA-I distribution among lipoproteins. In summary, high plasma le vels of SAA in the absence of a generalized acute phase response did not re sult in reduction of HDL cholesterol or apoA-I in mice, suggesting that the re are components of the acute phase response other than SAA expression tha t may directly influence HDL metabolism.