Table 2 Representative clinical trials that targeting TLR4 and related pathways in myocardial inflammation

From: The emerging role of Toll-like receptor 4 in myocardial inflammation

Diseases

Treatment

Effects

AM

APN

Inhibition of TLR4-MyD88-NF-κB-TNF-α/IL-6 and MyD88-independent apoptosis pathways63

AM

LPS

Induction of TLR4 and production of the anti-inflammatory chemokine CXCL1/KC61

MI

Metformin

Suppression of TLR4-MyD88-NF-κB-TNF-α/IL-6 pathway19

Myocardial I/R injury

Pterostilbene

Suppression of TLR4-NF-∂B-TNF-α pathway, NO production, and attenuation of inflammatory responses and cell apoptosis73

Myocardial I/R injury

AsIV

Downregulation of TLR4-NF-κB-TNF-α/IL-1β pathway and inhibition of cell apoptosis70

Myocardial I/R injury

Eritoran

Pretreatment with eritoran suppresses TLR4-MyD88-TRAF6-TAK1-JNK and TLR4-MyD88-TRAF6-TAK1-IKKs-NF-∂B pathways and further decreases expression of TNF-α, IL-1β, and IL-675

Myocardial I/R injury

Follistatin

Pretreatment with follistatin inhibits the TLR4-MyD88-dependent pathway and reduces apoptosis and infarcts of cardiac myocytes76

Myocardial I/R injury

GP

A shift from a predominant TLR4-NF-κB pathway to the PI3K/Akt pathway; cardioprotective effects79

  1. Abbreviations: AM, autoimmune myocarditis; APN, adiponectin; AsIV, astragaloside IV; GP, glucan phosphate; IL, interleukin; IKK, inhibitory κB kinase; I/R, ischemia/reperfusion; JNK, c-Jun N-terminal kinase; LPS, lipopolysaccharide; MI, myocardial infarction; MyD88, myeloid differentiation factor 88; NF-κB, nuclear factor-κB; NO, nitric oxide; PI3K, phosphatidylinositol 3-kinase; TLR4, Toll-like receptor; TNF-α, tumor necrosis factor-α; TRAF6, tumor necrosis factor receptor-associated factor 6; TAK1, transforming growth factor-β-activated kinase 1
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