Differential expression of Toll-like receptor 4 and human monocyte subsets in acute myocardial infarction

Abstract 

Objective

To investigate the involvement of Toll-like receptor 4 (TLR4) expression on two monocyte subsets in the pathologic processes related to acute coronary syndrome. How monocytes, which have recently been shown to comprise two distinct subsets, mediate the process of coronary plaque rupture remains to be fully elucidated. Recent studies have shown that TLR4 is involved in monocyte activation of patients with accelerated forms of atherosclerosis.

Methods

We enrolled 65 patients with acute myocardial infarction (AMI, n=22), unstable angina pectoris (UAP, n=16), and stable angina pectoris (SAP, n=27) who underwent coronary angiography and 15 healthy controls. The expression of TLR4 on two monocyte subsets (CD14⁺CD16⁻ and CD14⁺CD16⁺) was measured by flow cytometry.

Results

In patients with AMI, TLR4 was more expressed on circulating CD14⁺CD16⁺ monocytes than on CD14⁺CD16⁻ monocytes (p<0.001). The expression levels of TLR4 on CD14⁺CD16⁺ monocytes were significantly elevated in patients with AMI compared with other 3 groups. TLR4 expression levels on CD14⁺CD16⁺ monocytes were significantly elevated at the culprit site compared with the systemic level (p=0.044). The up-regulation of TLR4 on admission was remarkably decreased 12 days after AMI (p<0.001). In addition, plasma levels of tumor necrosis factor-α were positively correlated with TLR4 expression levels on monocytes in patients with AMI (r=0.47, p=0.027).

Conclusion

TLR overexpression on CD14⁺CD16⁺ monocytes in AMI, as demonstrated both in the circulation and at the coronary culprit site, might be associated with the pathogenesis of AMI.

Keywords: Monocyte, TLR4, Acute myocardial infarction