TLR2 knockout in old mice significantly reduced myocardial infarct size to 21% compared to 56% in wild-type mice and improved cardiac function following ischemia and reperfusion injury.
Does TLR2 knockout reduce cardiac inflammatory response, adverse remodeling, and cardiac dysfunction following ischemia and reperfusion injury in aging mice?
Genetic ablation of TLR2 in aging mice attenuates hyper-inflammatory responses, reduces infarct size, and improves cardiac function following myocardial ischemia/reperfusion injury.
Absolute Event Rate: 21% vs 56%
p-value: p=<0.05
This study tested the hypothesis that Toll-like receptor 2 (TLR2) augments the inflammatory responses and adverse remodeling in aging hearts to exacerbate myocardial injury and cardiac dysfunction. Methods: Old (20-22 months old) and adult (4-6 months old) mice of C57BL/6 wild-type and TLR2 knockout (KO) were subjected to coronary artery ligation (30 minutes) and reperfusion (3 or 14 days). Left ventricle function was assessed using a pressure-volume microcatheter. Cardiac infarct size was determined by histology. Levels of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), matrix metalloproteinase 9 (MMP 9), and collagen I in non-ischemic myocardium were assessed by immunoblotting. Monocyte chemoattractant protein-1 (MCP-1), keratinocyte chemoattractant (KC), and interleukin-6 (IL-6) levels in ischemic and non-ischemic myocardium were measured by enzyme-linked immunosorbent assay (ELISA). TLR2 expression in the myocardium of untreated wild type mice was also measured by immunoblotting. Results: Higher levels of MCP-1, KC, IL-6 were induced in both ischemic and non-ischemic myocardium of old wild type mice at day 3 and 14 following ischemia/reperfusion (I/R) than those of adult wild type mice. The hyper-inflammatory responses to I/R in aging hearts were associated with elevated levels of myocardial TLR2. TLR2 KO markedly down-regulated the expression of MCP-1, KC, IL-6, ICAM-1 and VCAM-1 in aging hearts at day 3 and 14 following I/R. The down-regulated inflammatory activity in aging TLR2 KO hearts was associated with attenuated production of MMP 9 and collagen I at day 14 and resulted in reduced infarct size and improved cardiac function. Conclusion: Elevated expression of myocardial TLR2 contributes to the mechanism by which aging exacerbates the inflammatory responses, adverse remodeling and cardiac dysfunction following myocardial I/R in aging.
Zhai et al. (Thu,) conducted a other in Myocardial ischemia and reperfusion injury. TLR2 knockout vs. Wild-type was evaluated on Myocardial infarct size (% of left ventricle free wall) at day 14 in old mice (p=<0.05). TLR2 knockout in old mice significantly reduced myocardial infarct size to 21% compared to 56% in wild-type mice and improved cardiac function following ischemia and reperfusion injury.