MicroRNA-Dependent Control of Serotonin-Induced Pulmonary Arterial Contraction
(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.
(Less)
- author
- organization
- publishing date
- 2017-08-11
- 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
- 2024-08-05 03:52:21
@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}}, }