Gender disparity in the role of TLR2 in post-ischemic myocardial inflammation and injury

It is unclear whether Toll-like receptor (TLR) 2 plays a role in post-ischemic myocardial inflammatory response and cardiac dysfunction in both males and females. Permanent ischemia was induced in male and female C57BL/6J (wild-type, WT) and TLR2 knockout (KO) mice. Infarct size and left ventricular (LV) function were analyzed at day 7. Myocardial levels of monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1), as well as neutrophil infiltration, were assessed at day 3, and mononuclear cell accumulation was determined at day 7. Lower MCP-1 and ICAM-1 levels, and reduced leukocyte accumulation correlated with smaller infarct size and improved LV function in male TLR2 KO mice. Female WT mice exhibited attenuated myocardial inflammatory response and injury, and TLR2 KO in females did not provide a protective effect although myocardial TLR2 levels in female WT mice were unaltered, and their cardiac cells responded to bacterial TLR2 agonist properly. TLR2 KO in male mice reduced post-ischemic myocardial inflammatory response, resulting in smaller infarct sizes and improved cardiac function. However, TLR2 KO was not beneficial in female mice. The gender disparity in the role of TLR2 in post-ischemic myocardial inflammatory response and myocardial injury suggests that interception with TLR2 signaling may have therapeutic potentials only in males.