持续性高血压可诱导血管紧张素II、C-反应蛋白等促炎因子的分泌，炎症反应进一步加重了压力超负荷下的心室重构和心力衰竭，其潜在的病理分子机制尚不明确。我们前期研究发现，CXCR6受体在趋化心脏炎症细胞浸润的过程中发挥重要作用，缺血-再灌注导致心肌损伤和心室重构在CXCR6基因敲除小鼠明显减轻。国外最新报道CXCR6在剪切应力下可致动脉血栓和血管重构，提示CXCR6可能是研究压力超负荷诱导心室重构的重要靶点。此外，我们还发现TGF-β信号通路的激活促进压力超负荷下心肌重塑的过程。据此，本项目拟从研究CXCR6受体出发，构建CXCR6敲除小鼠的压力超负荷（TAC）模型，探讨CXCR6在血管损伤与心肌重塑中的作用和联系，重点阐明CXCR6介导炎症因子的旁分泌效应和对TGF-β下游信号调控的分子机制，明确CXCR6敲除对于改善压力超负荷引起心室重构的保护作用，为预防和治疗结构性心脏病寻找合适的靶点。

The proinflammatory cytokines such as Angiotensin II and C- reactive protein are increased during hypertension, which further promote the progress of pressure overload-induced ventricular remodeling and heart failure.However, the underlying molecular mechanism is poorly understood. Our previous study showed that CXCR6 receptor played an important role in inducing the infiltration of inflammatory cells in myocardium during ischemia/reperfusion (I/R) injury. CXCR6 knockout significantly improved I/R-induced myocardial injury and ventricular remodeling. The recent study also reported that shear stress stimulated CXCR6 receptor and the later mediated arterial thrombosis and vascular remodeling, which indicated a possible role of CXCR6 in pressure overload-induced cardiac remodeling. In addition, we revealed that pressure overload-induced ventricular remodeling was dependent on the activation of TGF-β signaling pathway. Based on these results, we aim to investigate the potential mechanism of pressure overload-induced ventricular remodeling in CXCR6-/- mice with a TAC model. The present study stresses on the effects and relations of CXCR6 on vascular injury and myocardial remodeling, and CXCR6-mediated paracrine effect of inflammatory cytokines on TGF-β downstream signaling. To illustrate the protective role of CXCR6 deficiency in improving pressure overload-induced ventricular remodeling. The current experiment may shed light on the novel target for the fundamental study and clinical therapy of myocardial remodeling.