The role of plasma phospholipid transfer protein (PLTP) in HDL remodeling in acute-phase patients.
During reverse cholesterol transport plasma phospholipid transfer protein (PLTP) converts high density lipoprotein(3) (HDL(3)) into two new subpopulations, HDL(2)-like particles and pre-beta-HDL. The acute-phase response is accompanied with dramatic changes in lipid metabolism including alterations in HDL concentration, composition, and thereby its function as a substrate for HDL remodeling proteins in circulation. To evaluate how acute-phase HDL (AP-HDL) functions in PLTP-mediated HDL conversion, we collected plasma samples from patients with severe acute-phase response (n=17), and from healthy controls (n=30). Subsequently, total HDL (1.063<d<1.21 g/ml) was isolated from patients and controls and incubated in the absence and presence of purified PLTP. The results show that HDL isolated from the acute-phase patients is converted by PLTP in vitro in a corresponding manner as normal HDL. In the combined population, C-reactive protein correlated significantly with lecithin-cholesterol acyltransferase (LCAT) activity (r=-0.53), cholesterol ester transfer protein activity (r=-0.80), PLTP activity (r=0.44), and PLTP mass (r=-0.66). When compared to the controls, the patients had 31% higher PLTP activity, but 52% lower PLTP mass leading to a 165% higher PLTP specific activity in the patients. The present data indicate that during the acute-phase response, plasma PLTP activity and mass are strongly affected by the lipoprotein distribution as well as lipid composition. We suggest that the decrease of HDL during the acute phase is caused by reduced LCAT and increased PLTP activities both increasing the plasma levels of lipid-poor apoA-I particles.
Pussinen
P J
PJ
National Public Health Institute, Department of Molecular Medicine, Biomedicum Helsinki, Helsinki, Finland. pirkko.pussinen@helsinki.fi
Metso
J
J
Malle
E
E
Barlage
S
S
Palosuo
T
T
Sattler
W
W
Schmitz
G
G
Jauhiainen
M
M
D000210:Acute-Phase Reaction / Q000097:blood*; D001692:Biological Transport; D002352:Carrier Proteins / Q000097:blood* / Q000737:chemistry / Q000302:isolation & purification; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D008565:Membrane Proteins / Q000097:blood* / Q000737:chemistry; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood; D049294:Phospholipid Transfer Proteins; D014461:Ultracentrifugation
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D008075:Lipoproteins, HDL; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; D007862:Phosphatidylcholine-Sterol O-Acyltransferase