Circulating Dipeptidyl Peptidase 3 Modulates Systemic and Renal Hemodynamics Through Cleavage of Angiotensin Peptides.

DPP3 protein, human angiotensin II blood pressure catecholamines circulatory failure procizumab renal blood flow renin–angiotensin system

Journal

Hypertension (Dallas, Tex. : 1979)
ISSN: 1524-4563
Titre abrégé: Hypertension
Pays: United States
ID NLM: 7906255

Informations de publication

Date de publication:
Apr 2024
Historique:
pubmed: 9 2 2024
medline: 9 2 2024
entrez: 9 2 2024
Statut: ppublish

Résumé

High circulating DPP3 (dipeptidyl peptidase 3) has been associated with poor prognosis in critically ill patients with circulatory failure. In such situation, DPP3 could play a pathological role, putatively via an excessive angiotensin peptides cleavage. Our objective was to investigate the hemodynamics changes induced by DPP3 in mice and the relation between the observed effects and renin-angiotensin system modulation. Ten-week-old male C57Bl/6J mice were subjected to intravenous injection of purified human DPP3 or an anti-DPP3 antibody (procizumab). Invasive blood pressure and renal blood flow were monitored throughout the experiments. Circulating angiotensin peptides and catecholamines were measured and receptor blocking experiment performed to investigate the underlying mechanisms. DPP3 administration significantly increased renal blood flow, while blood pressure was minimally affected. Conversely, procizumab led to significantly decreased renal blood flow. Angiotensin peptides measurement and an AT1R (angiotensin II receptor type 1) blockade experiment using valsartan demonstrated that the renovascular effect induced by DPP3 is due to reduced AT1R activation High circulating DPP3 increases renal blood flow due to reduced AT1R activation via decreased concentrations of circulating angiotensin peptides while blood pressure is maintained by concomitant endogenous catecholamines release.

Sections du résumé

BACKGROUND UNASSIGNED
High circulating DPP3 (dipeptidyl peptidase 3) has been associated with poor prognosis in critically ill patients with circulatory failure. In such situation, DPP3 could play a pathological role, putatively via an excessive angiotensin peptides cleavage. Our objective was to investigate the hemodynamics changes induced by DPP3 in mice and the relation between the observed effects and renin-angiotensin system modulation.
METHODS UNASSIGNED
Ten-week-old male C57Bl/6J mice were subjected to intravenous injection of purified human DPP3 or an anti-DPP3 antibody (procizumab). Invasive blood pressure and renal blood flow were monitored throughout the experiments. Circulating angiotensin peptides and catecholamines were measured and receptor blocking experiment performed to investigate the underlying mechanisms.
RESULTS UNASSIGNED
DPP3 administration significantly increased renal blood flow, while blood pressure was minimally affected. Conversely, procizumab led to significantly decreased renal blood flow. Angiotensin peptides measurement and an AT1R (angiotensin II receptor type 1) blockade experiment using valsartan demonstrated that the renovascular effect induced by DPP3 is due to reduced AT1R activation
CONCLUSIONS UNASSIGNED
High circulating DPP3 increases renal blood flow due to reduced AT1R activation via decreased concentrations of circulating angiotensin peptides while blood pressure is maintained by concomitant endogenous catecholamines release.

Identifiants

DOI: 10.1161/HYPERTENSIONAHA.123.21913 PMID: 38334001
pubmed: 38334001
doi: 10.1161/HYPERTENSIONAHA.123.21913
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

927-935

Déclaration de conflit d'intérêts

The Cardiovascular Markers in Stress Conditions Research Group is supported by a research grant from 4TEEN4 Pharmaceuticals GmbH, which allowed salary support for 2 authors (A. Picod and M. Genest). K. Santos is used by 4TEEN4 Pharmaceuticals. A. Mebazaa received speaker’s honoraria from Abbott, Novartis, Orion, Roche, and Servier, and fees as a member of the advisory board and steering committee from Cardiorentis, Adrenomed, MyCartis, Neurotronik, and Sphingotec. The other authors report no conflicts.

Auteurs

Adrien Picod (A)

Institut National de la Santé et de la Recherche Médicale UMR-S 942 MASCOT - Paris - Cité University, Paris, France (A.P., M.G., J.C., N.J., M.Z., N.A., H.N., A.M., F.A.).
ORCID: 0000-0002-0639-5598

Sandrine Placier (S)

INSERM UMR-S 1155 CORAKID - Paris - Sorbonne University, France (S.P., S.G., C.C.).

Magali Genest (M)

Institut National de la Santé et de la Recherche Médicale UMR-S 942 MASCOT - Paris - Cité University, Paris, France (A.P., M.G., J.C., N.J., M.Z., N.A., H.N., A.M., F.A.).

Jacques Callebert (J)

Institut National de la Santé et de la Recherche Médicale UMR-S 942 MASCOT - Paris - Cité University, Paris, France (A.P., M.G., J.C., N.J., M.Z., N.A., H.N., A.M., F.A.).
Department of Biochemistry and Molecular Biology, Lariboisière - Saint Louis Hospitals (J.C.), APHP, Paris, France.
ORCID: 0000-0002-5622-851X

Nathan Julian (N)

Institut National de la Santé et de la Recherche Médicale UMR-S 942 MASCOT - Paris - Cité University, Paris, France (A.P., M.G., J.C., N.J., M.Z., N.A., H.N., A.M., F.A.).
Department of Anesthesiology and Intensive Care, Lariboisière - Saint Louis Hospitals (N.J., A.M.), APHP, Paris, France.
ORCID: 0000-0003-4144-7549

Maxime Zalc (M)

Institut National de la Santé et de la Recherche Médicale UMR-S 942 MASCOT - Paris - Cité University, Paris, France (A.P., M.G., J.C., N.J., M.Z., N.A., H.N., A.M., F.A.).
Department of Anesthesiology and Intensive Care, Mondor Hospital (M.Z.), APHP, Paris, France.
Paris Est - Créteil University, France (M.Z.).
ORCID: 0000-0001-7284-7030

Noma Assad (N)

Institut National de la Santé et de la Recherche Médicale UMR-S 942 MASCOT - Paris - Cité University, Paris, France (A.P., M.G., J.C., N.J., M.Z., N.A., H.N., A.M., F.A.).

Hugo Nordin (H)

Institut National de la Santé et de la Recherche Médicale UMR-S 942 MASCOT - Paris - Cité University, Paris, France (A.P., M.G., J.C., N.J., M.Z., N.A., H.N., A.M., F.A.).

Karine Santos (K)

4TEEN4 Pharmaceuticals Gmbh, Hennigsdorf, Germany (K.S.).
ORCID: 0000-0003-0467-7708

Stéphane Gaudry (S)

INSERM UMR-S 1155 CORAKID - Paris - Sorbonne University, France (S.P., S.G., C.C.).
Sorbonne - Paris Nord University, France (S.G.).
Medical and Surgical Intensive Care Unit, Avicenne Hospital, APHP, Bobigny, France (S.G.).

Christos Chatziantoniou (C)

INSERM UMR-S 1155 CORAKID - Paris - Sorbonne University, France (S.P., S.G., C.C.).

Alexandre Mebazaa (A)

Institut National de la Santé et de la Recherche Médicale UMR-S 942 MASCOT - Paris - Cité University, Paris, France (A.P., M.G., J.C., N.J., M.Z., N.A., H.N., A.M., F.A.).
Department of Anesthesiology and Intensive Care, Lariboisière - Saint Louis Hospitals (N.J., A.M.), APHP, Paris, France.
ORCID: 0000-0001-8715-7753

Feriel Azibani (F)

Institut National de la Santé et de la Recherche Médicale UMR-S 942 MASCOT - Paris - Cité University, Paris, France (A.P., M.G., J.C., N.J., M.Z., N.A., H.N., A.M., F.A.).

Classifications MeSH