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Updated: Jul 1, 2026

Cholesterol Efflux Assay
Published on: March 6, 2012
Reduced leucocyte cholesteryl ester transfer protein expression in acute coronary syndromes
D Ye1, A O Kraaijeveld, R W Grauss
1Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands.
Insights
Acute coronary syndromes (ACS) reduce leucocyte cholesterol ester transfer protein (CETP) expression. This impairment in CETP production is linked to increased inflammation and may play a role in ACS development.
Area of Science:
- Cardiovascular Biology
- Atherosclerosis Research
- Immunology
Background:
- Cholesterol ester transfer protein (CETP) is crucial for HDL cholesterol metabolism.
- Leukocytes, including macrophages, synthesize CETP, but its role in atherosclerosis remains unclear.
Purpose of the Study:
- To investigate the impact of acute coronary syndromes (ACS) on leukocyte CETP expression.
- To explore the relationship between leukocyte CETP levels and the inflammatory status in ACS patients.
Main Methods:
- Peripheral blood mononuclear cells (PBMCs) were isolated from unstable angina pectoris (UAP) patients and healthy controls.
- CETP expression was analyzed in human PBMCs and in CETP transgenic mice following myocardial infarction.
Main Results:
- UAP patients showed significantly lower CETP mRNA and protein in PBMCs upon admission compared to controls.
- CETP levels increased by 180 days post-admission, correlating with reduced inflammation.
- Myocardial infarction in mice also led to down-regulated leukocyte CETP expression.
Conclusions:
- Reduced leukocyte CETP expression is associated with UAP in humans and myocardial infarction in mice.
- Impaired CETP production in leukocytes may contribute to the enhanced inflammatory state seen in ACS pathogenesis.
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.
Research Design:
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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