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Spontaneous activity and stretch‐induced contractile differentiation are reduced in vascular smooth muscle of miR‐143/145 knockout mice
Author(s) -
Bhattachariya A.,
Dahan D.,
Ekman M.,
Boettger T.,
Braun T.,
Swärd K.,
Hellstrand P.,
Albinsson S.
Publication year - 2015
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12536
Subject(s) - microrna , vascular smooth muscle , knockout mouse , depolarization , microbiology and biotechnology , calcium in biology , calcium channel , medicine , endocrinology , calcium , biology , chemistry , anatomy , intracellular , receptor , biochemistry , smooth muscle , gene
Aim Stretch is essential for maintaining the contractile phenotype of vascular smooth muscle cells, and small non‐coding micro RNA s are known to be important in this process. Using a Dicer knockout model, we have previously reported that microRNAs are essential for stretch‐induced differentiation and regulation of L‐type calcium channel expression. The aim of this study was to investigate the importance of the smooth muscle‐enriched miR‐143/145 micro RNA cluster for stretch‐induced differentiation of the portal vein. Methods Contractile force and depolarization‐induced calcium influx were determined in portal veins from wild‐type and miR‐143/145 knockout mice. Stretch‐induced contractile differentiation was investigated by determination of mRNA expression following organ culture for 24 h under longitudinal load by a hanging weight. Results In the absence of miR‐143/145, stretch‐induced mRNA expression of contractile markers in the portal vein was reduced. This was associated with decreased amplitude of spontaneous activity and depolarization‐induced contractile and intracellular calcium responses, while contractile responses to 5‐ HT were largely maintained. We found that these effects correlated with a reduced basal expression of the pore‐forming subunit of L‐type calcium channels and an increased expression of Ca MKII δ and the transcriptional repressor DREAM . Conclusion Our results suggest that the micro RNA ‐143/145 cluster plays a role in maintaining stretch‐induced contractile differentiation and calcium signalling in the portal vein. This may have important implications for the use of these micro RNA s as therapeutic targets in vascular disease.