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

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Outzen, Emilie M ; Zaki, Marina ; Mehryar, Rahila ; Abdolalizadeh, Bahareh ; Sajid, Waseem ; Boonen, Harrie C M ; Sams, Anette ; Sheykhzade, Majid. / Lipopolysaccharides, but not Angiotensin ll, lnduces Direct Pro-lnflammatory Effects in Cultured Mouse Arteries and Human Endothelial and Vascular Smooth Muscle Cells. In: Basic & clinical pharmacology & toxicology. 2017 ; Vol. 120, No. 4. pp. 335-347.

Bibtex

@article{83d5463c2721491586eab4de58172ea6,
title = "Lipopolysaccharides, but not Angiotensin ll, lnduces Direct Pro-lnflammatory Effects in Cultured Mouse Arteries and Human Endothelial and Vascular Smooth Muscle Cells",
abstract = "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.",
keywords = "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",
author = "Outzen, {Emilie M} and Marina Zaki and Rahila Mehryar and Bahareh Abdolalizadeh and Waseem Sajid and Boonen, {Harrie C M} and Anette Sams and Majid Sheykhzade",
note = "{\textcopyright} 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).",
year = "2017",
doi = "10.1111/bcpt.12697",
language = "English",
volume = "120",
pages = "335--347",
journal = "Basic & Clinical Pharmacology & Toxicology Online",
issn = "1742-7843",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "4",

}

RIS

TY - JOUR

T1 - Lipopolysaccharides, but not Angiotensin ll, lnduces Direct Pro-lnflammatory Effects in Cultured Mouse Arteries and Human Endothelial and Vascular Smooth Muscle Cells

AU - Outzen, Emilie M

AU - Zaki, Marina

AU - Mehryar, Rahila

AU - Abdolalizadeh, Bahareh

AU - Sajid, Waseem

AU - Boonen, Harrie C M

AU - Sams, Anette

AU - Sheykhzade, Majid

N1 - © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Adult

KW - Angiotensin II/pharmacology

KW - Animals

KW - Blotting, Western

KW - Cell Culture Techniques

KW - Chemokine CCL2/metabolism

KW - Dose-Response Relationship, Drug

KW - Endothelium, Vascular/drug effects

KW - Human Umbilical Vein Endothelial Cells

KW - Humans

KW - Interleukin-6/metabolism

KW - Lipopolysaccharides/pharmacology

KW - Male

KW - Mesenteric Arteries/drug effects

KW - Mice, Inbred C57BL

KW - Muscle Contraction/drug effects

KW - Muscle, Smooth, Vascular/cytology

KW - Organ Culture Techniques

KW - Phosphorylation

KW - Transcription Factor RelA/metabolism

U2 - 10.1111/bcpt.12697

DO - 10.1111/bcpt.12697

M3 - Journal article

C2 - 27813367

VL - 120

SP - 335

EP - 347

JO - Basic & Clinical Pharmacology & Toxicology Online

JF - Basic & Clinical Pharmacology & Toxicology Online

SN - 1742-7843

IS - 4

ER -

ID: 55604465