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Deficiency of Complement C3a and C5a receptors Does Not Prevent Angiotensin II-Induced Hypertension and Hypertensive End-Organ Damage

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Deficiency of Complement C3a and C5a receptors Does Not Prevent Angiotensin II-Induced Hypertension and Hypertensive End-Organ Damage. / Bode, Marlies; Herrnstadt, Georg R; Dreher, Leonie; Ehnert, Nicolas; Kirkerup, Pia; Lindenmeyer, Maja T; Meyer-Schwesinger, Catherine F; Ehmke, Heimo; Köhl, Jörg; Huber, Tobias B; Krebs, Christian F; Steinmetz, Oliver M; Wiech, Thorsten; Wenzel, Ulrich O.

In: HYPERTENSION, Vol. 81, No. 1, 01.2024, p. 138-150.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Bode, M, Herrnstadt, GR, Dreher, L, Ehnert, N, Kirkerup, P, Lindenmeyer, MT, Meyer-Schwesinger, CF, Ehmke, H, Köhl, J, Huber, TB, Krebs, CF, Steinmetz, OM, Wiech, T & Wenzel, UO 2024, 'Deficiency of Complement C3a and C5a receptors Does Not Prevent Angiotensin II-Induced Hypertension and Hypertensive End-Organ Damage', HYPERTENSION, vol. 81, no. 1, pp. 138-150. https://doi.org/10.1161/HYPERTENSIONAHA.123.21599

APA

Bode, M., Herrnstadt, G. R., Dreher, L., Ehnert, N., Kirkerup, P., Lindenmeyer, M. T., Meyer-Schwesinger, C. F., Ehmke, H., Köhl, J., Huber, T. B., Krebs, C. F., Steinmetz, O. M., Wiech, T., & Wenzel, U. O. (2024). Deficiency of Complement C3a and C5a receptors Does Not Prevent Angiotensin II-Induced Hypertension and Hypertensive End-Organ Damage. HYPERTENSION, 81(1), 138-150. https://doi.org/10.1161/HYPERTENSIONAHA.123.21599

Vancouver

Bode M, Herrnstadt GR, Dreher L, Ehnert N, Kirkerup P, Lindenmeyer MT et al. Deficiency of Complement C3a and C5a receptors Does Not Prevent Angiotensin II-Induced Hypertension and Hypertensive End-Organ Damage. HYPERTENSION. 2024 Jan;81(1):138-150. https://doi.org/10.1161/HYPERTENSIONAHA.123.21599

Bibtex

@article{697d668b584b40849d5e3d08033b6508,
title = "Deficiency of Complement C3a and C5a receptors Does Not Prevent Angiotensin II-Induced Hypertension and Hypertensive End-Organ Damage",
abstract = "BACKGROUND: Complement may drive the pathology of hypertension through effects on innate and adaptive immune responses. Recently an injurious role for the anaphylatoxin receptors C3aR (complement component 3a receptor) and C5aR1 (complement component 5a receptor) in the development of hypertension was shown through downregulation of Foxp3+ (forkhead box protein 3) regulatory T cells. Here, we deepen our understanding of the therapeutic potential of targeting both receptors in hypertension.METHODS: Data from the European Renal cDNA Bank, single cell sequencing and immunohistochemistry were examined in hypertensive patients. The effect of C3aR or C3aR/C5aR1 double deficiency was assessed in two models of Ang II (angiotensin II)-induced hypertension in knockout mice.RESULTS: We found increased expression of C3aR, C5aR1 and Foxp3 cells in kidney biopsies of patients with hypertensive nephropathy. Expression of both receptors was mainly found in myeloid cells. No differences in blood pressure, renal injury (albuminuria, glomerular filtration rate, glomerular and tubulointerstitial injury, inflammation) or cardiac injury (cardiac fibrosis, heart weight, gene expression) between control and mutant mice was discerned in C3aR-/- as well as C3aR/C5aR1-/- double knockout mice. The number of renal Tregs was not decreased in Ang II as well as in DOCA salt induced hypertension.CONCLUSIONS: Hypertensive nephropathy in mice and men is characterized by an increase of renal regulatory T cells and enhanced expression of anaphylatoxin receptors. Our investigations do not corroborate a role for C3aR/C5aR1 axis in Ang II-induced hypertension hence challenging the concept of anaphylatoxin receptor targeting in the treatment of hypertensive disease.",
keywords = "Animals, Humans, Mice, Anaphylatoxins, Angiotensin II, Complement C3a/metabolism, Complement C5a/metabolism, Forkhead Transcription Factors, Hypertension/genetics, Mice, Knockout, Receptor, Anaphylatoxin C5a/genetics, Receptors, Complement/genetics",
author = "Marlies Bode and Herrnstadt, {Georg R} and Leonie Dreher and Nicolas Ehnert and Pia Kirkerup and Lindenmeyer, {Maja T} and Meyer-Schwesinger, {Catherine F} and Heimo Ehmke and J{\"o}rg K{\"o}hl and Huber, {Tobias B} and Krebs, {Christian F} and Steinmetz, {Oliver M} and Thorsten Wiech and Wenzel, {Ulrich O}",
year = "2024",
month = jan,
doi = "10.1161/HYPERTENSIONAHA.123.21599",
language = "English",
volume = "81",
pages = "138--150",
journal = "HYPERTENSION",
issn = "0194-911X",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

RIS

TY - JOUR

T1 - Deficiency of Complement C3a and C5a receptors Does Not Prevent Angiotensin II-Induced Hypertension and Hypertensive End-Organ Damage

AU - Bode, Marlies

AU - Herrnstadt, Georg R

AU - Dreher, Leonie

AU - Ehnert, Nicolas

AU - Kirkerup, Pia

AU - Lindenmeyer, Maja T

AU - Meyer-Schwesinger, Catherine F

AU - Ehmke, Heimo

AU - Köhl, Jörg

AU - Huber, Tobias B

AU - Krebs, Christian F

AU - Steinmetz, Oliver M

AU - Wiech, Thorsten

AU - Wenzel, Ulrich O

PY - 2024/1

Y1 - 2024/1

N2 - BACKGROUND: Complement may drive the pathology of hypertension through effects on innate and adaptive immune responses. Recently an injurious role for the anaphylatoxin receptors C3aR (complement component 3a receptor) and C5aR1 (complement component 5a receptor) in the development of hypertension was shown through downregulation of Foxp3+ (forkhead box protein 3) regulatory T cells. Here, we deepen our understanding of the therapeutic potential of targeting both receptors in hypertension.METHODS: Data from the European Renal cDNA Bank, single cell sequencing and immunohistochemistry were examined in hypertensive patients. The effect of C3aR or C3aR/C5aR1 double deficiency was assessed in two models of Ang II (angiotensin II)-induced hypertension in knockout mice.RESULTS: We found increased expression of C3aR, C5aR1 and Foxp3 cells in kidney biopsies of patients with hypertensive nephropathy. Expression of both receptors was mainly found in myeloid cells. No differences in blood pressure, renal injury (albuminuria, glomerular filtration rate, glomerular and tubulointerstitial injury, inflammation) or cardiac injury (cardiac fibrosis, heart weight, gene expression) between control and mutant mice was discerned in C3aR-/- as well as C3aR/C5aR1-/- double knockout mice. The number of renal Tregs was not decreased in Ang II as well as in DOCA salt induced hypertension.CONCLUSIONS: Hypertensive nephropathy in mice and men is characterized by an increase of renal regulatory T cells and enhanced expression of anaphylatoxin receptors. Our investigations do not corroborate a role for C3aR/C5aR1 axis in Ang II-induced hypertension hence challenging the concept of anaphylatoxin receptor targeting in the treatment of hypertensive disease.

AB - BACKGROUND: Complement may drive the pathology of hypertension through effects on innate and adaptive immune responses. Recently an injurious role for the anaphylatoxin receptors C3aR (complement component 3a receptor) and C5aR1 (complement component 5a receptor) in the development of hypertension was shown through downregulation of Foxp3+ (forkhead box protein 3) regulatory T cells. Here, we deepen our understanding of the therapeutic potential of targeting both receptors in hypertension.METHODS: Data from the European Renal cDNA Bank, single cell sequencing and immunohistochemistry were examined in hypertensive patients. The effect of C3aR or C3aR/C5aR1 double deficiency was assessed in two models of Ang II (angiotensin II)-induced hypertension in knockout mice.RESULTS: We found increased expression of C3aR, C5aR1 and Foxp3 cells in kidney biopsies of patients with hypertensive nephropathy. Expression of both receptors was mainly found in myeloid cells. No differences in blood pressure, renal injury (albuminuria, glomerular filtration rate, glomerular and tubulointerstitial injury, inflammation) or cardiac injury (cardiac fibrosis, heart weight, gene expression) between control and mutant mice was discerned in C3aR-/- as well as C3aR/C5aR1-/- double knockout mice. The number of renal Tregs was not decreased in Ang II as well as in DOCA salt induced hypertension.CONCLUSIONS: Hypertensive nephropathy in mice and men is characterized by an increase of renal regulatory T cells and enhanced expression of anaphylatoxin receptors. Our investigations do not corroborate a role for C3aR/C5aR1 axis in Ang II-induced hypertension hence challenging the concept of anaphylatoxin receptor targeting in the treatment of hypertensive disease.

KW - Animals

KW - Humans

KW - Mice

KW - Anaphylatoxins

KW - Angiotensin II

KW - Complement C3a/metabolism

KW - Complement C5a/metabolism

KW - Forkhead Transcription Factors

KW - Hypertension/genetics

KW - Mice, Knockout

KW - Receptor, Anaphylatoxin C5a/genetics

KW - Receptors, Complement/genetics

U2 - 10.1161/HYPERTENSIONAHA.123.21599

DO - 10.1161/HYPERTENSIONAHA.123.21599

M3 - SCORING: Journal article

C2 - 37909169

VL - 81

SP - 138

EP - 150

JO - HYPERTENSION

JF - HYPERTENSION

SN - 0194-911X

IS - 1

ER -