Background: Toll-like receptors, the most characterized innate immune receptors, have recently been demonstrated to play an important role in coronary atherosclerotic disease and diabetes mellitus (DM). TLR3 and TLR4 are known to act as anti-inflammatory and pro-inflammatory factors respectively in multi-factorial inflammatory disease states. However, there is less research about TLR3 and TLR4 expression in percutaneous transluminal coronary intervention (PCI) patients, particularly those with type 2 diabetes mellitus (DM2).
Methods: We examined TLR3 and TLR4 expression and their downstream signaling pathway in PCI patients with (n=31) or without (n=32) DM2 compared with controls (n=35).
Results: TLR3 and downstream anti-inflammatory factors (IRF-3, INF-β and IL-10) were significantly down-regulated in PCI patients with or without DM2 compared with controls, as determined by the quantification of both mRNA and protein. In contrast, TLR4 and downstream proinflammatory factors (MyD88 and TNF-α) were up-regulated in PCI patients with or without DM2 compared with controls.
Conclusions: Patients undergoing PCI were shown to have a TLR-dependent pro-inflammatory state, mediated by a downregulation of TLR3 pathway, and upregulation of TLR4. This occurred in both with or without type 2 diabetes mellitus compared with controls in this research. The inflammatory imbalance observed in PCI patients was exacerbated in patients with DM2, consistent with a likely contribution of DM2 to the inflammatory state of coronary atherosclerotic disease, via impact on the innate immune response. This data supports the potential of TLRs as a novel therapeutic target in diabetics with coronary atherosclerotic disease.
Keywords: Inflammatory unbalance; Percutaneous transluminal coronary intervention; Toll-like receptors; Type 2 mellitus diabetes.
Copyright © 2014. Published by Elsevier B.V.