Histamine receptor agonist alleviates severe cardiorenal damages by eliciting anti-inflammatory programming.
H3 agonist
animal model
anti-inflammation
cardiorenal damages
histamine
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
11 02 2020
11 02 2020
Historique:
pubmed:
30
1
2020
medline:
12
5
2020
entrez:
30
1
2020
Statut:
ppublish
Résumé
Heart failure and chronic kidney disease are major causes of morbidity and mortality internationally. Although these dysfunctions are common and frequently coexist, the factors involved in their relationship in cardiorenal regulation are still largely unknown, mainly due to a lack of detailed molecular targets. Here, we found the increased plasma histamine in a preclinical mouse model of severe cardiac dysfunction, that had been cotreated with angiotensin II (Ang II), nephrectomy, and salt (ANS). The ANS mice exhibited impaired renal function accompanied with heart failure, and histamine depletion, by the genetic inactivation of histidine decarboxylase in mice, exacerbated the ANS-induced cardiac and renal abnormalities, including the reduction of left ventricular fractional shortening and renal glomerular and tubular injuries. Interestingly, while the pharmacological inhibition of the histamine receptor H3 facilitated heart failure and kidney injury in ANS mice, administration of the H3 agonist immethridine (Imm) was protective against cardiorenal damages. Transcriptome analysis of the kidney and biochemical examinations using blood samples illustrated that the increased inflammation in ANS mice was alleviated by Imm. Our results extend the pharmacological use of H3 agonists beyond the initial purposes of its drug development for neurogenerative diseases and have implications for therapeutic potential of H3 agonists that invoke the anti-inflammatory gene expression programming against cardiorenal damages.
Identifiants
pubmed: 31992639
pii: 1909124117
doi: 10.1073/pnas.1909124117
pmc: PMC7022214
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Histamine Agonists
0
Protective Agents
0
Receptors, Histamine H3
0
Histamine
820484N8I3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3150-3156Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 the Author(s). Published by PNAS.
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