Mikolajczyk Tomasz P, Szczepaniak Piotr, Vidler Francesca, Maffia Pasquale, Graham Gerard J, Guzik Tomasz J
Department of Internal and Agricultural Medicine, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland; Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
Department of Internal and Agricultural Medicine, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland.
Pharmacol Ther. 2021 Jul;223:107799. doi: 10.1016/j.pharmthera.2020.107799. Epub 2020 Dec 24.
Hypertension is associated with immune cells activation and their migration into the kidney, vasculature, heart and brain. These inflammatory mechanisms are critical for blood pressure regulation and mediate target organ damage, creating unique novel targets for pharmacological modulation. In response to angiotensin II and other pro-hypertensive stimuli, the expression of several inflammatory chemokines and their receptors is increased in the target organs, mediating homing of immune cells. In this review, we summarize the contribution of key inflammatory chemokines and their receptors to increased accumulation of immune cells in target organs and effects on vascular dysfunction, remodeling, oxidative stress and fibrosis, all of which contribute to blood pressure elevation. In particular, the role of CCL2, CCL5, CXCL8, CXCL9, CXCL10, CXCL11, CXCL16, CXCL1, CX3CL1, XCL1 and their receptors in the context of hypertension is discussed. Recent studies have tested the efficacy of pharmacological or genetic targeting of chemokines and their receptors on the development of hypertension. Promising results indicate that some of these pathways may serve as future therapeutic targets to improve blood pressure control and prevent target organ consequences including kidney failure, heart failure, atherosclerosis or cognitive impairment.
高血压与免疫细胞激活及其向肾脏、血管、心脏和大脑的迁移有关。这些炎症机制对血压调节至关重要，并介导靶器官损伤，从而产生了药理学调节的独特新靶点。响应血管紧张素II和其他促高血压刺激，几种炎症趋化因子及其受体在靶器官中的表达增加，介导免疫细胞归巢。在本综述中，我们总结了关键炎症趋化因子及其受体对靶器官中免疫细胞积累增加的贡献，以及对血管功能障碍、重塑、氧化应激和纤维化的影响，所有这些都导致血压升高。特别讨论了CCL2、CCL5、CXCL8、CXCL9、CXCL10、CXCL11、CXCL16、CXCL1、CX3CL1、XCL1及其受体在高血压背景下的作用。最近的研究测试了趋化因子及其受体的药理学或基因靶向对高血压发展的疗效。有前景的结果表明，其中一些途径可能成为未来的治疗靶点，以改善血压控制并预防包括肾衰竭、心力衰竭、动脉粥样硬化或认知障碍在内的靶器官后果。
