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MicroRNA-Dependent Control of Serotonin-Induced Pulmonary Arterial Contraction

Dahan, Diana LU ; Hien Tran, Thi LU ; Tannenberg, Philip ; Ekman, Mari LU ; Rippe, Catarina LU ; Boettger, Thomas ; Braun, Thomas ; Tran-Lundmark, Karin LU ; Tran, P and Swärd, Karl LU , et al. (2017) In Journal of Vascular Research 54(4). p.246-256
Abstract

Background: Serotonin (5-HT) is considered to play a role in pulmonary arterial hypertension by regulating vascular remodeling and smooth muscle contractility. Here, arteries from mice with inducible and smooth muscle-specific deletion of Dicer were used to address mechanisms by which microRNAs control 5-HT-induced contraction. Methods: Mice were used 5 weeks after Dicer deletion, and pulmonary artery contractility was analyzed by wire myography. Results: No change was seen in right ventricular systolic pressure following dicer deletion, but systemic blood pressure was reduced. Enhanced 5-HT-induced contraction in Dicer KO pulmonary arteries was associated with increased 5-HT2A receptor mRNA expression whereas 5-HT1B and 5-HT2B receptor... (More)

Background: Serotonin (5-HT) is considered to play a role in pulmonary arterial hypertension by regulating vascular remodeling and smooth muscle contractility. Here, arteries from mice with inducible and smooth muscle-specific deletion of Dicer were used to address mechanisms by which microRNAs control 5-HT-induced contraction. Methods: Mice were used 5 weeks after Dicer deletion, and pulmonary artery contractility was analyzed by wire myography. Results: No change was seen in right ventricular systolic pressure following dicer deletion, but systemic blood pressure was reduced. Enhanced 5-HT-induced contraction in Dicer KO pulmonary arteries was associated with increased 5-HT2A receptor mRNA expression whereas 5-HT1B and 5-HT2B receptor mRNAs were unchanged. Contraction by the 5-HT2A agonist TCB-2 was increased in Dicer KO as was the response to the 5-HT2B agonist BW723C86. Effects of Src and protein kinase C inhibition were similar in control and KO arteries, but the effect of inhibition of Rho kinase was reduced. We identified miR-30c as a potential candidate for 5-HT2A receptor regulation as it repressed 5-HT2A mRNA and protein. Conclusion: Our findings show that 5-HT receptor signaling in the arterial wall is subject to regulation by microRNAs and that this entails altered 5-HT2A receptor expression and signaling.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
microRNA, Pulmonary arteries, Serotonin
in
Journal of Vascular Research
volume
54
issue
4
pages
11 pages
publisher
Karger
external identifiers
  • pmid:28796998
  • pmid:28796998
  • wos:000409104300007
  • scopus:85027187706
ISSN
1018-1172
DOI
10.1159/000478013
language
English
LU publication?
yes
id
5661add7-cf23-4194-9677-331ef9e64fa0
date added to LUP
2017-09-04 13:38:36
date last changed
2024-02-29 21:21:02
@article{5661add7-cf23-4194-9677-331ef9e64fa0,
  abstract     = {{<p>Background: Serotonin (5-HT) is considered to play a role in pulmonary arterial hypertension by regulating vascular remodeling and smooth muscle contractility. Here, arteries from mice with inducible and smooth muscle-specific deletion of Dicer were used to address mechanisms by which microRNAs control 5-HT-induced contraction. Methods: Mice were used 5 weeks after Dicer deletion, and pulmonary artery contractility was analyzed by wire myography. Results: No change was seen in right ventricular systolic pressure following dicer deletion, but systemic blood pressure was reduced. Enhanced 5-HT-induced contraction in Dicer KO pulmonary arteries was associated with increased 5-HT2A receptor mRNA expression whereas 5-HT1B and 5-HT2B receptor mRNAs were unchanged. Contraction by the 5-HT2A agonist TCB-2 was increased in Dicer KO as was the response to the 5-HT2B agonist BW723C86. Effects of Src and protein kinase C inhibition were similar in control and KO arteries, but the effect of inhibition of Rho kinase was reduced. We identified miR-30c as a potential candidate for 5-HT2A receptor regulation as it repressed 5-HT2A mRNA and protein. Conclusion: Our findings show that 5-HT receptor signaling in the arterial wall is subject to regulation by microRNAs and that this entails altered 5-HT2A receptor expression and signaling.</p>}},
  author       = {{Dahan, Diana and Hien Tran, Thi and Tannenberg, Philip and Ekman, Mari and Rippe, Catarina and Boettger, Thomas and Braun, Thomas and Tran-Lundmark, Karin and Tran, P and Swärd, Karl and Albinsson, Sebastian}},
  issn         = {{1018-1172}},
  keywords     = {{microRNA; Pulmonary arteries; Serotonin}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{4}},
  pages        = {{246--256}},
  publisher    = {{Karger}},
  series       = {{Journal of Vascular Research}},
  title        = {{MicroRNA-Dependent Control of Serotonin-Induced Pulmonary Arterial Contraction}},
  url          = {{http://dx.doi.org/10.1159/000478013}},
  doi          = {{10.1159/000478013}},
  volume       = {{54}},
  year         = {{2017}},
}