Role of the Anaphylatoxin Receptor C5aR2 in Angiotensin II-Induced Hypertension and Hypertensive End-Organ Damage
Abstract 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...
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Veröffentlicht in: | American journal of hypertension 2024-09, Vol.37 (10), p.810-825 |
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Hauptverfasser: | , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Abstract
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 |
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ISSN: | 0895-7061 1941-7225 1941-7225 |
DOI: | 10.1093/ajh/hpae082 |