Abstract 19130: Acute Inducible Cardiac Ischemia is Related With a Decrease in Toll-Like Receptor 2 and 4 Response
Background: Toll-Like Receptor (TLR) activation induces inflammation upon ligand binding by either pathogens or endogenous molecules. We previously showed that TLR dependent leukocyte responsiveness is acutely attenuated when patients undergo percutaneous coronary intervention (PCI) or vascular surgery. Furthermore, we showed that cytokine release following whole blood TLR-2 and −4 stimulation is negatively correlated with fractional flow reserve, suggesting that chronic ischemia is related with the capability of TLRs to enhance pro-inflammatory cytokine production. In the current study we assessed the association between pre-existent and acutely inducible ischemia on TLR-2 and -4 response in patients undergoing myocardial single photon emission computed tomography (SPECT).
Methods: Whole blood samples were obtained in 100 patients immediately before and after myocardial stress induction for SPECT imaging. TLR2, TLR4 and CD11b expression on monocytes were measured with flow cytometry. IL-8 levels were determined after overnight whole blood stimulation with Pam3Cys (TLR2) and lipopolysaccharide (LPS; TLR4). The SPECT outcome was categorized to three groups: reversible defect, irreversible defect or no defect.
Results: IL-8 production before myocardial stress induction was not associated to SPECT outcome. However, a significant decrease in IL-8 production following TLR stimulation was observed in samples obtained after stress during SPECT investigation (4605±473 vs 3122±461 for Pam3Cys 500 ng/ml; p<0.001). This decrease was also observed for TLR4 (1.70±0.2 vs 1.61±0.16, p=0.001) and CD11b expression (82±1.9 vs 72.4±1.8, p<0.001). Interestingly, the percentage decrease in TLR response was higher in patients with a reversible defect (TLR4 induced IL-8: reversible defect 31.6% decrease vs. irreversible defect 15.24% decrease vs. no defect 15.39% decrease; p=0.035).
Conclusion: TLR-2 and -4 dependent leukocyte responsiveness are not higher in patients with pre-existent myocardial ischemia. However, acute ischemia is associated with a decrease in TLR-2 and -4 response. These results point to a regulating role of TLR responsiveness in order to prevent excessive inflammatory events known to occur during acute ischemia.
- © 2010 by American Heart Association, Inc.