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 A(2) (sPLA(2)-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.


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 sPLA(2)-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, sPLA(2)-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.
Jahangiri
Anisa
A
Department of Internal Medicine, Division of Endocrinology and Molecular Medicine, University of Kentucky, Lexington, KY, USA. anisa.jahangiri@uky.edu
de Beer
Maria C
MC
Noffsinger
Victoria
V
Tannock
Lisa R
LR
Ramaiah
Chandrashekar
C
Webb
Nancy R
NR
van der Westhuyzen
Deneys R
DR
de Beer
Frederick C
FC
D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000097:blood; D000210:Acute-Phase Reaction / Q000097:blood / Q000209:etiology*; D016632:Apolipoprotein A-I / Q000097:blood; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D002784:Cholesterol / Q000097:blood*; D053480:Cholesterol Ester Transfer Proteins / Q000097:blood; D002846:Chromatography, Affinity; D054501:Group II Phospholipases A2 / Q000097:blood; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood*; D008264:Macrophages / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000378:metabolism; D013997:Time Factors
C577836:ABCA1 protein, human; C419353:ABCG1 protein, human; C505693:APOA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008075:Lipoproteins, HDL; D011994:Recombinant Proteins; D000685:Serum Amyloid A Protein; D002784:Cholesterol; D054501:Group II Phospholipases A2