Joint first authors
TLR4 expression on monocyte subsets in myocardial infarction
Article first published online: 28 DEC 2012
© 2012 The Association for the Publication of the Journal of Internal Medicine
Journal of Internal Medicine
Volume 273, Issue 3, pages 294–305, March 2013
How to Cite
TLR4 expression on monocyte subsets in myocardial infarction. J Intern Med 2013; 273: 294–305., , , , (University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK).
- Issue published online: 15 FEB 2013
- Article first published online: 28 DEC 2012
- Accepted manuscript online: 3 NOV 2012 08:46AM EST
- monocyte subsets;
- myocardial infarction;
- Toll-like receptor 4
Monocyte toll-like receptor 4 (TLR4) has been implicated in the pathogenesis of atherosclerosis with increased levels in myocardial infarction. The aim of this study was to assess the numbers of TLR4+ monocytes in each monocyte subset in MI, the expression of TLR4 and association with markers of monocyte activation, inflammation, myocardial damage and postmyocardial infarction (MI) cardiac contractility.
Surface expression of TLR4 and numbers of TLR4-expressing monocytes were quantified by flow cytometry of venous blood in 50 patients with ST-elevation MI (STEMI), 48 with non-STEMI (NSTEMI) and 40 with stable coronary artery disease (CAD). These parameters were measured on days 1, 3, 7 and 30 post-MI in STEMI patients. Three monocyte subsets were defined as CD14++ CD16− CCR2+ (Mon1), CD14++ CD16+ CCR2+ (Mon2) and CD14+ CD16++ CCR2− (Mon3). Plasma inflammatory cytokines were assessed using cytometric bead arrays.
There was a significant increase in counts of TLR4+ Mon1 and Mon2 in STEMI patients and TLR4+ Mon2 in NSTEMI patients compared with controls with CAD. Monocyte TLR4+ expression was similar between the groups, and was not changed during follow-up in STEMI patients. Plasma interleukin-6 (IL6) levels correlated positively with TLR4+ Mon2 count (r = 0.54, P < 0.001), but negatively with TLR4 expression on Mon2 (r = −0.33, P = 0.021).
Following treatment of acute MI, TLR4 expression by individual monocyte subsets is unchanged. An increase in TLR4+ Mon1 and Mon2 count in patients with STEMI and TLR+ Mon2 count in those with NSTEMI is due to an increase in monocyte subset count and not to changes in TLR4 expression. Monocyte counts but not TLR4 expression correlate positively with plasma IL6 levels. We suggest that TLR4 expression may not be a reliable marker of monocyte activation in MI.