HDL remodeling during the acute phase response

Objective - The purpose of this study was to examine the interactive action of serum amyloid A (SAA), group IIA secretory phospholipase A₂ (sPLA₂-IIA), and cholesteryl ester transfer protein (CETP) on HDL remodeling and cholesterol efflux during the acute phase (AP) response elicited in humans after cardiac surgery. Methods and Results - Plasma was collected from patients before (pre-AP), 24 hours after (AP-1 d), and 5 days after cardiac surgery (AP-5 d). SAA levels were increased 16-fold in AP-1 d samples. The activity of sPLA₂-IIA was increased from 77.7±38.3 U/mL (pre-AP) to 281.4±57.1 U/mL (AP-1 d; P<0.001). CETP mass and activity reduction was commensurate to the reduction of HDL cholesterol levels. The combined action of SAA, sPLA₂-IIA, and CETP in vitro markedly remodeled HDL with the generation of lipid-poor apoA-I from both pre-AP and AP-1 d HDL. The net result of this remodeling was a relative preservation of ABCA1- and ABCG1-dependent cholesterol efflux during the acute phase response. Conclusions - Our results show that the many and complex changes in plasma proteins during the acute phase response markedly remodel HDL with functional implications, particularly the relative retention of cholesterol efflux capacity.