Acute coronary syndrome reduces leucocyte CETP expression up to 6-fold, with recovery tracking reduced inflammation, confirmed in CETP transgenic mice (J Intern Med 2008)

Original title: Reduced leucocyte cholesteryl ester transfer protein expression in acute coronary syndromes

J Intern Med · 6 September 2008 · 7

Ye D, Kraaijeveld AO, Grauss RW, Willems SM, van Vark-van der Zee LC, de Jager SC, Jauhiainen M, Kuivenhoven JA, Dallinga-Thie GM, Atsma DE, Hogendoorn PC, Biessen EA et al.

Peripheral blood mononuclear cells were isolated from hospitalized patients with unstable angina pectoris (Braunwald class IIIB) at admission and 180 days later, and from CETP transgenic mice after coronary artery ligation, to study leucocyte cholesteryl ester transfer protein (CETP) expression in acute coronary syndrome. At admission, patients showed approximately 3- to 6-fold lower CETP mRNA (P < 0.01) and nearly absent CETP protein compared with healthy age- and sex-matched controls, while CETP mRNA and protein were significantly higher at 180 days than at admission (P < 0.01), correlating with reduced inflammatory status after treatment. Leucocyte CETP mRNA was similarly down-regulated after coronary artery ligation in CETP transgenic mice, correlating with increased serum amyloid A. This is the first report that unstable angina in humans and myocardial infarction in CETP transgenic mice are associated with reduced leucocyte CETP expression.

Original abstract

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.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.