Preconditioning by toll-like receptor 2 agonist Pam3CSK4 reduces CXCL1-dependent leukocyte recruitment in murine myocardial ischemia/reperfusion injury*

Abstract

Preconditioning by TLR2 agonist Pam3CSK4 reduces myocardial infarct size after myocardial ischemia/reperfusion. One of the mechanisms involved is a diminished chemokine release from cardiomyocytes, which subsequently limits leukocyte infiltration.

Toll-Like Receptor 2/6 Agonist Macrophage-Activating Lipopeptide-2 Promotes Reendothelialization and Inhibits Neointima Formation After Vascular Injury

“…32 In contrast, unique and selective pretreatment with TLR2 or TLR4 ligands reduced infarct size and improved cardiac function after ischemia/reperfusion. 33,34 To date, different TLR ligands (eg, TLR9) have been described to accelerate wound healing involving angiogenesis by endothelial cells. 35 These data suggest an ambivalent role for TLRs in cardiovascular pathology.…”

The essential roles of Toll-like receptor signaling pathways in sterile inflammatory diseases

“…The signaling of TLR2/IL-23/IL-17 [110] and CD36-TLR2 [111] played an important role in response to cerebral I/R and suppression of TLR2 signaling might be a valuable approach to minimize post-ischemic inflammation and brain injury. Some studies showed the protective role of TLR2 in myocardial I/R injury based on the observations that pre-conditioning by TLR2 agonist Pam3CSK4 reduced the injury [112], and that activation of TLR2 enhanced mesenchymal stem cell-associated myocardial recovery and vascular endothelial growth factor production following acute I/R injury [113]. Adverse effects on myocardial remodeling were found in TLR2 −/− mice with marked left ventricular dilation [114], further confirming the beneficial effects of TLR2 signal in this model.…”

Toll-like Receptors in the Vascular System: Sensing the Dangers Within

“…Nevertheless, TLR activation has been found to be advantageous before ischemic insults. Low doses of the TLR2 agonists Pam3CSK4 (a synthetic diacylated lipopeptide) or peptidoglycan before myocardial ischemia/reperfusion injury reduced infarct size, cardiac function, and the susceptibility of the myocardium to damage (Ha et al, 2010;Mersmann et al, 2010). Peptidoglycan stimulation increased TLR2 tyrosine phosphorylation and enhanced association of the p85 subunit of phosphoinositide 3-kinase with TLR2 (Ha et al, 2010).…”