Characterization of the Expression of TLR2 (Toll-like Receptor 2) and TLR4 on Circulating Monocytes in Coronary Artery Disease

Abstract

TLRs are receptors involved in the recognition of pathogens by the innate immune system, and TLR2 and TLR4 play important roles in the activation of monocytes. A total of 105 consecutive patients who underwent coronary angiography comprised of 46 with stable effort angina (SA), 41 with unstable angina (UA), and 18 with no significant CAD (CNT) were enrolled. The baseline expression levels of TLR2 and TLR4 on monocytes in peripheral blood mononuclear cells (PBMCs) were determined by flowcytometric analysis. Since TLR2 expression has been reported to be regulated by TLR4 signaling, we cultured PBMCs with or without lipopolysaccharide (LPS, 1 µ µ µ µ µg/ ml). At baseline, TLR4 levels (mean of fluorescence intensity ) in SA (145 ± ± ± ± ± 58, p < 0.05) and UA (164 ± ± ± ± ± 65, p < 0.01) were higher than those in CNT (107 ± ± ± ± ± 37). As for TLR2, levels were higher in UA (108 ± ± ± ± ± 36, p < 0.05) than in SA (94 ± ± ± ± ± 18) and CNT (87 ± ± ± ± ± 22). After stimulation with LPS, TLR2 levels increased in SA but decreased in UA. In conclusions, TLR4 levels increased in both SA and UA. Monocytes in UA were characterized by elevated TLR2 levels and unresponsiveness of the TLR2 levels to TLR4 stimulation. J Atheroscler Thromb, 2005; 12: 53-60.

Toll-Like Receptor-2 Mediates Inflammation and Matrix Degradation in Human Atherosclerosis

“…Patients with acute coronary syndromes but not stable angina have an increased expression of TLR-2 and -4 on circulating monocytes. 21,22 Such increase in expression does not always result in enhanced TLR signaling. 21,23,24 Therefore, there is currently little information on whether TLR signaling is protective or detrimental at lesion sites in human atherosclerosis.…”

Is Toll-like receptor responsiveness a marker and predictor of coronary artery disease?

“…The expression of TLR4 on monocytes has been shown to correlate to TNFα and IL-6 release after LPS stimulation [11]. Also, surface expression of TLR2 and TLR4 on circulating monocytes has been shown to be increased in acute myocardial infarction and unstable angina patients compared to healthy control patients [9,10]. The predictive power of TLR surface expression, however, could be questioned [16].…”

“…Polymorphisms in the TLR4 gene have also been suggested to be associated with cardiovascular disease [2]. Surface expression of TLR2 and TLR4 on circulating monocytes has been shown to be increased in acute myocardial infarction and unstable angina patients compared to healthy control patients [9][10][11]. Given that TLR expression has been implicated atherosclerosis progression, it is likely that the magnitude of TLR induced release of inflammatory cytokines, i.e.…”

Type 2 Diabetes, Immunity and Cardiovascular Risk: A Complex Relationship

“…Furthermore, TLR4 has been found in atherosclerotic lesions and at the site of plaque rupture in patients with MI (Ishikawa et al, 2008), and its expression is increased in thrombi from patients with acute coronary syndromes (Wyss et al, 2010;Yonekawa et al, 2011). Moreover, several studies showed that circulating monocytes of patients with atherosclerotic disease exhibit higher expression of TLR2 and TLR4 as compared to healthy individuals (Geng et al, 2006;Kuwahata et al, 2010;Mizoguchi et al, 2007;Shiraki et al, 2006), and an enhanced TLR signaling has been demonstrated in monocytes of patients with ACS (Ashida et al, 2005;Versteeg et al, 2008).…”