Local expression of Toll-like receptor 4 at the site of ruptured plaques in patients with acute myocardial infarction

Abstract

Several reports suggest that a chronic inflammatory process plays a key role in coronary artery plaque instability and subsequent occlusive thrombosis. In a previous study, we found that TLR4 (Toll-like receptor 4) mediates the synthesis of cytokines in circulating monocytes of patients with AMI (acute myocardial infarction); however, it remains unclear whether TLRs are expressed at the site of the ruptured plaque in these patients. The aim of the present study was to determine whether TLR2 and TLR4 are expressed at the site of ruptured plaques in patients with AMI and to compare this with systemic levels. The study included 62 patients with AMI, 20 patients with SA (stable angina) and 32 subjects with a normal coronary angiogram (control). Local samples from the site of the ruptured plaque were taken from patients with AMI using aspiration catheterization. Systemic blood samples from the aorta were taken from patients with AMI and SA and controls. Systemic levels of TLR2 and TLR4 were higher in patients with AMI than in patients with SA and controls. In patients with AMI, local TLR4 levels were higher than systemic levels. There was no significant difference in TLR2 levels between local and systemic samples. TLR4 immunostaining was positive in infiltrating macrophages in ruptured plaque material. Cardiac events were observed in 16 patients with AMI at the time of the 6-month follow-up study. Local and systemic levels of TLR4 were higher in patients with AMI with cardiac events than in those without. These results indicate an increase in monocytic TLR4 expression not only in the systemic circulation, but also at the site of plaque rupture. In conclusion, expression of both systemic and local plaque TLR4 may be one of the mechanisms responsible for the pathogenesis of AMI.

7 Monocyte subpopulations in patients following st-elevation myocardial infarction: implications for post-infarction left ventricular remodelling and clinical outcomes

“…TLR4 was also increased systematically in patients following myocardial infarction (MI) and locally at site of plaque rupture, yet suggesting that monocyte TLR4 has a role in plaque destabilization and rupture (Ishikawa et al, 2008). TLR4 was increased in both stable and unstable angina, with a congruent increase in TLR2 in the unstable state only (Ashida et al, 2005).…”

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

“…TLR4, whose endogenous ligand is ox-LDL (Xu et al, 2001), is highly expressed in SMC of atherosclerotic vessels, where it has been associated with the induction of a proinflammatory phenotype (Loppnow et al, 2008;Otsui et al, 2007). 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).…”

Monocytes in Acute Coronary Syndromes

“…21 Together these cells orchestrate local mobilization of monocytes in reparative processes in response to the ischemia and inflammation which is seen in ACS. 22 Plasma MCP-1 levels increase as early as 3 hours after the onset of chest pain, reach their maximum at 24 hours, and remain elevated for at least 7 days. 23 Interestingly, the majority of studies on MCP-1 genetic polymorphism failed to find any association with the risk of MI (supplemental Table III).…”