Procalcitonin mediates vascular dysfunction in obesity.

Animals Calcitonin Gene-Related Peptide / metabolism Calcitonin Receptor-Like Protein / metabolism Dipeptidyl Peptidase 4 / metabolism Dipeptidyl-Peptidase IV Inhibitors / pharmacology Endothelial Cells / metabolism Endothelium, Vascular Inflammation / metabolism Mice Nitric Oxide / metabolism Obesity / metabolism Procalcitonin Reactive Oxygen Species / metabolism Sitagliptin Phosphate / pharmacology Vasodilation
Endothelial dysfunction Inflammation Obesity Perivascular fat Procalcitonin

Journal

Life sciences
ISSN: 1879-0631
Titre abrégé: Life Sci
Pays: Netherlands
ID NLM: 0375521

Informations de publication

Date de publication:
15 Oct 2022
Historique:
received: 26 07 2022
revised: 13 08 2022
accepted: 14 08 2022
pubmed: 24 8 2022
medline: 13 10 2022
entrez: 23 8 2022
Statut: ppublish

Résumé

Obesity is accompanied by a chronic low-grade inflammation associated with endothelial dysfunction and vascular complications. Procalcitonin is a marker of inflammation, secreted by adipose tissue and elevated in obese subjects. We here investigated whether visceral or perivascular fat-derived procalcitonin is a target to improve obesity-induced endothelial dysfunction. Procalcitonin expression was identified by Western blot. Murine endothelial cells were isolated using CD31-antibody-coated magnetic beads and reactive oxygen species and nitric oxide (NO) determined by H2DCF- or DAF-FM diacetate loading. Endothelium-dependent vasorelaxation was analyzed using pressure myography of murine arterioles. Calcitonin gene-related peptide (CGRP) was used to activate the calcitonin receptor-like receptor (CRLR)/RAMP1 complex and olcegepant or the dipeptidyl-peptidase 4 (DPP4) inhibitor sitagliptin to block procalcitonin signaling or activation. In addition to visceral adipose tissue, procalcitonin was present in perivascular and epicardial tissue. In concentrations typical for obesity, procalcitonin doubled reactive oxygen species formation and decreased endothelial nitric oxide production in murine endothelial cells. Intravenous delivery of procalcitonin to mice in obesity-associated concentrations impaired endothelium-dependent vasorelaxation in a CRLR/RAMP1-dependent manner and antagonized CGRP-induced endothelial NO release in vitro. Use of CRLR/RAMP1-receptor antagonist olcegepant counteracted procalcitonin effects on vasodilation, nitric oxide production and reactive oxygen species formation. Similarly, blocking procalcitonin activation by the DPP4 inhibitor sitagliptin antagonized endothelial procalcitonin effects. Procalcitonin, liberated either from visceral or perivascular adipose tissue, contributes to endothelial dysfunction by antagonizing CGRP signaling in obesity. Targeting hyperprocalcitonemia may be a means to preserve endothelial function and reduce comorbidity burden in obese subjects.

Identifiants

DOI: 10.1016/j.lfs.2022.120889 PMID: 35998685
pubmed: 35998685
pii: S0024-3205(22)00589-6
doi: 10.1016/j.lfs.2022.120889
pii:
doi:

Substances chimiques

Calcitonin Receptor-Like Protein 0
Dipeptidyl-Peptidase IV Inhibitors 0
Procalcitonin 0
Reactive Oxygen Species 0
Nitric Oxide 31C4KY9ESH
Dipeptidyl Peptidase 4 EC 3.4.14.5
Calcitonin Gene-Related Peptide JHB2QIZ69Z
Sitagliptin Phosphate TS63EW8X6F

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

120889

Informations de copyright

Copyright © 2022 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare that there are no conflicts of interest.

Auteurs

Laura Brabenec (L)

Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany.

Katharina E M Hellenthal (KEM)

Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany.

Melanie Müller (M)

Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany.

Sebastian Kintrup (S)

Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany.

Finnja Zurek-Leffers (F)

Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany.

Marina Kardell (M)

Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany.

Mandy Otto (M)

Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany.

Nana-Maria Wagner (NM)

Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany. Electronic address: nmwagner@uni-muenster.de.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Procalcitonin mediates vascular dysfunction in obesity.
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Neuropeptides › Peptide relié au gène de la calcitonine › Procalcitonin mediates vascular dysfunction in obesity.
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs couplés aux protéines G › Protéine apparentée au récepteur de la calcitonine › Procalcitonin mediates vascular dysfunction in obesity.
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Antigènes de différenciation › Antigènes de différenciation des lymphocytes T › Dipeptidyl peptidase 4 › Procalcitonin mediates vascular dysfunction in obesity.
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Hypoglycémiants › Inhibiteurs de la dipeptidyl-peptidase IV › Procalcitonin mediates vascular dysfunction in obesity.
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules endothéliales › Procalcitonin mediates vascular dysfunction in obesity.
questionsmedicales.fr › Tissus › Épithélium › Endothélium › Endothélium vasculaire › Procalcitonin mediates vascular dysfunction in obesity.
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Procalcitonin mediates vascular dysfunction in obesity.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Procalcitonin mediates vascular dysfunction in obesity.
questionsmedicales.fr › Produits chimiques inorganiques › Composés de l'oxygène › Oxydes › Oxydes d'azote › Monoxyde d'azote › Procalcitonin mediates vascular dysfunction in obesity.
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Obésité › Procalcitonin mediates vascular dysfunction in obesity.
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Précurseurs de protéines › Procalcitonine › Procalcitonin mediates vascular dysfunction in obesity.
questionsmedicales.fr › Produits chimiques inorganiques › Composés de l'oxygène › Espèces réactives de l'oxygène › Procalcitonin mediates vascular dysfunction in obesity.
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pyrazines › Phosphate de sitagliptine › Procalcitonin mediates vascular dysfunction in obesity.
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiologiques cardiovasculaires › Hémodynamique › Vasodilatation › Procalcitonin mediates vascular dysfunction in obesity.