Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Lipopolysaccharides, but not Angiotensin ll, lnduces Direct Pro-lnflammatory Effects in Cultured Mouse Arteries and Human Endothelial and Vascular Smooth Muscle Cells

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Drug-related challenges following primary total hip and knee arthroplasty

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Validation of registration of pharmacological treatment in the Danish Hip and Knee Arthroplasty Registers

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Camostat mesylate against SARS-CoV-2 and COVID-19-Rationale, dosing and safety

    Research output: Contribution to journalReviewResearchpeer-review

  4. Postponement of cardiovascular outcomes by statin use: A systematic review and meta-analysis of randomized clinical trials

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. The effects of CGRP in vascular tissue - Classical vasodilation, shadowed effects and systemic dilemmas

    Research output: Contribution to journalReviewResearchpeer-review

  2. CGRP in rat mesenteric artery and vein - receptor expression, CGRP presence and potential roles

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Understanding side-effects of anti-CGRP and anti-CGRP receptor antibodies

    Research output: Contribution to journalLetterResearchpeer-review

  4. Fluorescent Analogues of Human α-Calcitonin Gene-Related Peptide with Potent Vasodilator Activity

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Emilie M Outzen
  • Marina Zaki
  • Rahila Mehryar
  • Bahareh Abdolalizadeh
  • Waseem Sajid
  • Harrie C M Boonen
  • Anette Sams
  • Majid Sheykhzade
View graph of relations

Angiotensin II (Ang II) might induce pro-inflammatory effects directly in the vascular wall independently of its haemodynamic effects. The aim of our study was to investigate the putative direct pro-inflammatory and vasomotor effects of Ang II and compare to those of lipopolysaccharides (LPS) in mouse isolated mesenteric resistance-sized arteries (MRA) supported by experiments in cultured human primary endothelial and vascular smooth muscle cells. Results showed that 24-hr organ culture of mouse MRA with 10 nM Ang II had, unlike 100 ng/mL LPS, no effects on IL-6 or MCP-1 secretion, VCAM1 mRNA expression or endothelial function, while Ang II significantly decreased maximal vasomotor responses to phenylephrine. In support, 24-hr organ culture of mouse MRA significantly suppressed Agtr1a mRNA and augmented Tlr4 mRNA along with attenuated vasomotor responses to Ang II. Moreover, contrary to LPS and TNF-α, Ang II and [Sar1]-Ang II had no concentration- or time-dependent effects on IL-6 and MCP-1 secretion in human umbilical vein endothelial cells (HUVEC) and human aortic smooth muscle cells (HASMC). AGTR1 or AGTR2 mRNA expression was undetectable in HUVEC, whereas HASMC expressed only AGTR1 mRNA. In summary, contrary to previous studies and the observed effects of LPS, we could not demonstrate direct vascular pro-inflammatory effects of Ang II ex vivo or in vitro. As indicated by our results, down-regulation or desensitization of AT1 R during culture may explain our findings.

Original languageEnglish
JournalBasic & clinical pharmacology & toxicology
Volume120
Issue number4
Pages (from-to)335-347
Number of pages13
ISSN1742-7843
DOIs
Publication statusPublished - 2017
Externally publishedYes

    Research areas

  • Adult, Angiotensin II/pharmacology, Animals, Blotting, Western, Cell Culture Techniques, Chemokine CCL2/metabolism, Dose-Response Relationship, Drug, Endothelium, Vascular/drug effects, Human Umbilical Vein Endothelial Cells, Humans, Interleukin-6/metabolism, Lipopolysaccharides/pharmacology, Male, Mesenteric Arteries/drug effects, Mice, Inbred C57BL, Muscle Contraction/drug effects, Muscle, Smooth, Vascular/cytology, Organ Culture Techniques, Phosphorylation, Transcription Factor RelA/metabolism

ID: 55604465