Reduced leucocyte cholesteryl ester transfer protein expression in acute coronary syndromes.
OBJECTIVE
Cholesterol ester transfer protein (CETP) plays an important role in HDL cholesterol metabolism. Leucocytes, including monocyte-derived macrophages in the arterial wall synthesize and secrete CETP, but its role in atherosclerosis is unclear. The aim of the current study was to investigate the effect of acute coronary syndromes (ACS) on leucocyte CETP expression.


METHODS
Peripheral blood mononuclear cells (PBMCs) were freshly isolated from hospitalized ACS patients displaying Braunwald class IIIB unstable angina pectoris (UAP) on admission (t = 0) and at 180 days post inclusion (t = 180) for analysis of CETP expression. In addition, to prove the potential correlation between leucocyte CETP and ACS the effect of acute myocardial infarction on leucocyte CETP expression was studied in CETP transgenic mice.


RESULTS
Upon admission, UAP patients displayed approximately 3-6 fold (P < 0.01) lower CETP mRNA and nearly absent CETP protein expression in PBMCs, as compared to healthy age-/sex-matched controls. Interestingly, CETP mRNA and protein levels were significantly elevated in PBMCs isolated from UAP patients (both stabilized and refractory) at t = 180 as compared to t = 0 (P < 0.01), which was correlated with a reduced inflammatory status after medical treatment. In agreement with the data obtained in UAP patients, markedly down-regulated leucocyte CETP mRNA expression was observed after coronary artery ligation in CETP transgenic mice, which also correlated with increased serum amyloid A levels.


CONCLUSIONS
We are the first to report that episodes of UAP in humans and myocardial infarction in CETP transgenic mice are associated with reduced leucocyte CETP expression. We propose that the impairment in leucocyte CETP production is associated with an enhanced inflammatory status, which could be clinically relevant for the pathogenesis of ACS.
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Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands.
Kraaijeveld
A O
AO
Grauss
R W
RW
Willems
S M
SM
van Vark-van der Zee
L C
LC
de Jager
S C A
SC
Jauhiainen
M
M
Kuivenhoven
J A
JA
Dallinga-Thie
G M
GM
Atsma
D E
DE
Hogendoorn
P C W
PC
Biessen
E A L
EA
Van Berkel
T J C
TJ
Jukema
J W
JW
van Eck
M
M
D054058:Acute Coronary Syndrome / Q000276:immunology / Q000378:metabolism*; D000208:Acute Disease; D000368:Aged; D000818:Animals; D002784:Cholesterol / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins / Q000032:analysis* / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D023421:Models, Animal
D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D002784:Cholesterol