{Reference Type}: Journal Article
{Title}: Role of the anaphylatoxin receptor C5aR2 in angiotensin II induced hypertension and hypertensive end organ damage.
{Author}: Dreher L;Bode M;Ehnert N;Meyer-Schwesinger C;Wiech T;Köhl J;Huber TB;Freiwald T;Herrnstadt GR;Wenzel UO;
{Journal}: Am J Hypertens
{Volume}: 0
{Issue}: 0
{Year}: 2024 Jun 27
{Factor}: 3.08
{DOI}: 10.1093/ajh/hpae082
{Abstract}: <B>BACKGROUND: </B>Complement activation may facilitate hypertension through its effects on immune responses. The anaphylatoxin C5a, a major inflammatory effector, binds to the C5a receptor 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.<BR><B>METHODS: </B>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 kidneys of hypertensive patients. Finally, we examined the effect of Ang II induced hypertension in C5aR2-deficient mice.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>In summary, C5aR2 is mainly expressed on myeloid cells in the kidney in mice and humans but its deficiency has no effect in Ang II induced hypertensive injury.