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

The responsiveness of the innate immune system to microbial components depends on the expression of specific pattern recognition receptors such as the Toll-like receptors (TLRs) [1]. The TLR family of receptors has evolved to recognize pathogen associated molecular patterns such as lipopolysaccharide (LPS) on the surface of Gram negative bacteria (TLR4) and lipopeptides on Grampositive bacteria (TLR2), as well as viral nucleic acids such as such as doubleand single-stranded RNA (TLR3, TLR7 and TLR8). The TLRs can also recognize so called damage associated molecular patterns generated during tissue injury such as heat-shock proteins and extracellular matrix components including extra domain A of fibronectin [2]. Upon activation, the TLRs activate signals resulting in release of cytokines that promote and coordinate inflammation. Due to their central role in regulating inflammation the TLRs have been implicated in the pathogenesis of many diseases including cardiovascular disease. The bacterial lipid sensing TLR2 and TLR4 receptors have attracted much attention in atherosclerosis research. Targeted deletion in mouse models of experimental atherosclerosis have shown that TLR2, TLR4, and the intracellular adaptor molecule MyD88, all promote atherosclerosis development [3e7]. TLR2 and TLR4 are expressed in human atherosclerotic