以CD11b+VEGFR-3+单核细胞为靶点干预慢性高盐摄入诱导的高血压性左心室重塑进程

Mononuclear phagocytes infiltration in hypertensive target organ indicates their important role in the development of hypertension. Recent studies have demonstrated that monocytes could differentiate into lymphatic endothelial cells in the inflammatory environments. Moreover, our previous study also found that macrophages could promote lymphangiogenesis through tonicity responsive enhancer binding protein(TonEBP)/vascular endothelial growth factor-C (VEGF-C) signaling pathway in the chronic high salt intake induced hyperosmotic state, and upregulated this lymphangiogenesis effects could significantly improve hypertensive left ventricular remodeling. The present study was to observe the potency of CD11b+VEGFR-3+ monocyte subset transdifferentiating into lymphatic endothelial cells in the high salt environment. Then, demonstrate CD11b+VEGFR-3+ monocytes could trandifferentiate into lymphatic endothelial cells in the chronic high salt intake induced hypertension and hypertensive left ventricular remodeling process. Lastly, to investigate the influence of modulating the proportion and the number of this subset on blood pressure and hypertensive left ventricular remodeling. The results will be helpful to better understandinging the pathophysiological role of mononuclear phagocytes in hypertension and target organ damage, demonstrate a new mechanism of chronic high salt intake induced hypertension and hypertensive left ventricular remodeling which have potential clinical prospects.

在高血压的发展进程中，伴随着单核吞噬细胞（MP）向靶器官的浸润，提示MP在高血压发展过程中扮演着重要角色。新近研究表明，在炎症条件下，单核细胞可通过转分化作用参与淋巴管的生成。我们的前期工作也发现，在慢性高盐摄入引起的高渗条件下，巨噬细胞通过张力应答增强子结合蛋白（TonEBP）/血管内皮生长因子-C（VEGF-C）通路可引起淋巴管的增生，调节淋巴管的生成可改善高血压性左心室重塑。本项目观察高盐诱导下CD11b+ VEGFR-3+单核细胞向淋巴管内皮细胞转分化的潜能，阐明在慢性高盐摄入诱导的高血压及其左心室重塑过程中该亚群单核细胞可通过转分化作用参与淋巴管的生成，最后探讨调节该亚群的数量及比例对血压及高血压性左心室重塑的影响。预期结果有助于深入了解MP在高血压及其靶器官损伤中的病理生理学作用，旨在阐明一种慢性高盐摄入诱导的高血压及其左心室重塑的新机制，并具有潜在的临床应用价值。

慢性高盐摄入是高血压相关的心血管疾病恶化加重最重要的环境因素之一。长期的高盐摄入不仅可以引起血压水平的增高，还可以独立于血压引起靶器官的损伤。在高血压的发展进程中，伴随着单核吞噬细胞（MP）向靶器官的浸润，提示MP在高血压发展过程中扮演着重要角色。我们的前期工作也发现，在慢性高盐摄入引起的高渗条件下，巨噬细胞通过张力应答增强子结合蛋白（TonEBP）/血管内皮生长因子-C（VEGF-C）通路可引起淋巴管的增生，调节淋巴管的生成可改善高血压性左心室重塑。本项目旨在观察CD11b+VEGFR-3+单核细胞向淋巴管内皮细胞转分化的潜能，阐明在慢性高盐摄入诱导的高血压及其左心室重塑过程中该亚群单核细胞可通过转分化作用参与淋巴管的生成，并探讨调节该亚群的比例对血压及高血压性左心室重塑的影响。结果发现，长期的高盐饮食干预可使小鼠VEGFR-3+单核巨噬细胞向淋巴管内皮细胞转化，增加该亚群的比例可通过促进淋巴管的增生改善高盐摄入诱导的高血压性左心室重塑。此外，我们还对外周血单核细胞不同亚群与高血压性靶器官损伤的相关性进行了进一步探讨，观察土槿乙酸的免疫调节机制对单核巨噬细胞表型及高血压性左心室重塑的影响。本项目研究结果进一步阐明了固有免疫系统在高血压及其靶器官损伤中的作用，为进一步以调节固有免疫系统为基础的高血压及其靶器官损伤的防治研究提供了思路，具有潜在的临床应用价值。