Gender disparity in the role of TLR2 in post-ischemic myocardial inflammation and injury.
Gender disparity in the role of TLR2 in post-ischemic myocardial inflammation and injury.
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发表时间：
2015-07
影响因子：
0.1
通讯作者：
Jilin Li;L. Ao;Yufeng Zhai;J. Cleveland;D. Fullerton;Xianzhong Meng
中科院分区：
文献类型：
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作者：
Jilin Li;L. Ao;Yufeng Zhai;J. Cleveland;D. Fullerton;Xianzhong Meng
目前尚不清楚 Toll 样受体 (TLR) 2 是否在男性和女性缺血后心肌炎症反应和心功能障碍中发挥作用。在雄性和雌性 C57BL/6J（野生型，WT）和 TLR2 敲除（KO）小鼠中诱导永久性缺血。第 7 天分析梗死面积和左心室 (LV) 功能。第 3 天评估心肌单核细胞趋化蛋白 1 (MCP-1) 和细胞间粘附分子 1 (ICAM-1) 水平以及中性粒细胞浸润，第 7 天测定单核细胞积累。较低的 MCP-1 和 ICAM-1 水平以及白细胞积累减少与梗塞面积较小和改善相关雄性 TLR2 KO 小鼠的左心室功能。雌性WT小鼠表现出减弱的心肌炎症反应和损伤，尽管雌性WT小鼠的心肌TLR2水平没有改变，并且它们的心肌细胞对细菌TLR2激动剂有适当的反应，但雌性TLR2 KO并没有提供保护作用。雄性小鼠中 TLR2 敲除可减少缺血后心肌炎症反应，从而缩小梗塞面积并改善心脏功能。然而，TLR2 KO 对雌性小鼠没有益处。 TLR2 在缺血后心肌炎症反应和心肌损伤中的作用存在性别差异，这表明拦截 TLR2 信号传导可能仅对男性具有治疗潜力。
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.