无乳毒素受体 C5aR2 在血管紧张素 II 诱导的高血压和高血压终末器官损伤中的作用

IF 3.2 3区 医学 Q2 PERIPHERAL VASCULAR DISEASE
Leonie Dreher, Marlies Bode, Nicolas Ehnert, Catherine Meyer-Schwesinger, Thorsten Wiech, Jörg Köhl, Tobias B Huber, Tilo Freiwald, Georg R Herrnstadt, Ulrich O Wenzel
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引用次数: 0

摘要

背景:补体激活可通过对免疫反应的影响促进高血压。C5a是一种主要的炎症效应物质,可与C5a受体1和2(C5aR1、C5aR2)结合。我们最近发现,C5aR1-/-小鼠的高血压肾损伤有所减轻。C5aR2在高血压中的作用尚不清楚:方法:使用串联染料 Tomato-C5aR2 基因敲入报告小鼠来检测 C5aR2 在浸润和驻留肾细胞中的表达。在高血压患者肾脏的单细胞 RNAseq 数据集中分析了人类 C5aR2 的表达。最后,我们研究了 C5aR2 基因缺陷小鼠对 Ang II 诱导的高血压的影响:从报告小鼠肾脏分离的白细胞流式细胞分析显示,树突状细胞是主要的 C5aR2 表达群体(34%),其次是单核/巨噬细胞(30%)和中性粒细胞(14%)。使用共聚焦显微镜在常驻肾脏或心脏细胞中未检测到 C5aR2。在人类肾脏中,C5aR2 也主要存在于单核细胞、巨噬细胞和树突状细胞中,在高血压中的表达量明显更高(pConclusion):总之,C5aR2 主要在小鼠和人类肾脏的髓样细胞中表达,但其缺乏对 Ang II 诱导的高血压损伤没有影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Role of the Anaphylatoxin Receptor C5aR2 in Angiotensin II-Induced Hypertension and Hypertensive End-Organ Damage.

Backround: Complement activation may facilitate hypertension through its effects on immune responses. The anaphylatoxin C5a, a major inflammatory effector, binds to the C5a receptors 1 and 2 (C5aR1, C5aR2). We have recently shown that C5aR1-/- mice have reduced hypertensive renal injury. The role of C5aR2 in hypertension is unknown.

Methods: For examination of C5aR2 expression on infiltrating and resident renal cells a tandem dye Tomato-C5aR2 knock-in reporter mouse was used. Human C5aR2 expression was analyzed in a single-cell RNAseq data set from the kidneys of hypertensive patients. Finally, we examined the effect of angiotensin II-induced hypertension in C5aR2-deficient mice.

Results: Flow cytometric analysis of leukocytes isolated from kidneys of the reporter mice showed that dendritic cells are the major C5aR2-expressing population (34%) followed by monocyte/macrophages (30%) and neutrophils (14%). Using confocal microscopy C5aR2 was not detected in resident renal or cardiac cells. In the human kidney, C5aR2 was also mainly found in monocytes, macrophages, and dendritic cells with a significantly higher expression in hypertension (P < 0.05). Unilateral nephrectomy was performed followed by infusion of Ang II (0.75 ng/g/min) and a high salt diet in wildtype (n = 18) and C5aR2-deficient mice (n = 14). Blood pressure, renal injury (albuminuria, glomerular filtration rate, glomerular and tubulointerstitial injury, inflammation), and cardiac injury (cardiac fibrosis, heart weight, gene expression) did not differ between hypertensive wildtype and C5aR2-/- mice.

Conclusions: In summary, C5aR2 is mainly expressed in myeloid cells in the kidney in mice and humans but its deficiency has no effect on Ang II-induced hypertensive injury.

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来源期刊
American Journal of Hypertension
American Journal of Hypertension 医学-外周血管病
CiteScore
6.90
自引率
6.20%
发文量
144
审稿时长
3-8 weeks
期刊介绍: The American Journal of Hypertension is a monthly, peer-reviewed journal that provides a forum for scientific inquiry of the highest standards in the field of hypertension and related cardiovascular disease. The journal publishes high-quality original research and review articles on basic sciences, molecular biology, clinical and experimental hypertension, cardiology, epidemiology, pediatric hypertension, endocrinology, neurophysiology, and nephrology.
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