Role of Toll‐like receptor 4 in the initiation and progression of atherosclerotic disease

Abstract

The family of Toll-like receptors ( TLRs) initiates an innate immune response after recognition of pathogen-associated molecular patterns (PAMPs). Evidence is accumulating that TLRs, and particularly TLR4, are important players in the initiation and progression of atherosclerotic disease. Not only exogenous ligands but also endogenous ligands that are expressed during arterial injury are recognized by TLR4. Mouse knockout studies and epidemiological studies of human TLR4 polymorphisms have demonstrated that the TLR4 might play a role in the initiation and progression of atherosclerosis. This review will summarize the latest progression in research on the role of TLR4 in arterial occlusive disease In addition, the potential of intervention in TLR4 signalling to influence progression of atherosclerotic disease is discussed.

Thematic review series: The Immune System and Atherogenesis. Paying the price for pathogen protection: toll receptors in atherogenesis

“…Although atherosclerosis is certainly a multigenic disease, two gene-targeted knockouts in mice, the LDL receptor and apolipoprotein E, provide excellent models for study (36), and direct in vivo evidence exists that TLR signaling plays a role in atherosclerosis (37,38). Two groups have demonstrated that MyD88, one of the TLR intracellular signaling molecules, participates in atherosclerosis.…”

Wnt5a is expressed in murine and human atherosclerotic lesions

“…Our observation that Wnt5a is expressed in the macrophagerich regions of murine atherosclerotic tissue and the fact that TLR-4 has been implicated in atherosclerosis (4,17,31) led us to investigate the ability of murine macrophages to express Wnt5a RNA upon stimulation of the TLR-4 signal transduction cascade. RAW264.7 (murine macrophages) were treated with various concentrations of LPS, a ligand for TLR-4.…”

“…There is a growing body of evidence that suggests that aberrant TLR expression or signaling is involved in pathological inflammation (1,6,24). Specifically, TLR-4, a TLR that recognizes lipopolysaccharide (LPS), has been implicated in atherosclerosis (7,17,31).…”

Heterozygous Arg753Gln Polymorphism of Human TLR-2 Impairs Immune Activation by Borrelia burgdorferi and Protects from Late Stage Lyme Disease

“…Incidence increased significantly over the last years, with Ͼ23,000 cases in the U.S. in 2002 (2). LD displays different clinical stages: erythema chronicum migrans (ECM) is associated with early localized infection; early disseminated infection commonly may include facial palsy as well as meningoencephalitis, the latter occurring more frequently in Europe as compared with the U.S. (3).…”