Advanced

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 Research1992-01-01+01:00 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.

(Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
in press
subject
keywords
microRNA, Pulmonary arteries, Serotonin
in
Journal of Vascular Research1992-01-01+01:00
pages
11 pages
publisher
Karger
external identifiers
  • scopus:85027187706
  • pmid:28796998
  • wos:000409104300007
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
2018-01-16 13:24:48
@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},
  keyword      = {microRNA,Pulmonary arteries,Serotonin},
  language     = {eng},
  month        = {08},
  pages        = {246--256},
  publisher    = {Karger},
  series       = {Journal of Vascular Research1992-01-01+01:00},
  title        = {MicroRNA-Dependent Control of Serotonin-Induced Pulmonary Arterial Contraction},
  url          = {http://dx.doi.org/10.1159/000478013},
  year         = {2017},
}