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Cardiovasc Res. 2017 May 1;113(6):681-691. doi: 10.1093/cvr/cvx032.

Shear stress-regulated miR-27b controls pericyte recruitment by repressing SEMA6A and SEMA6D.

Author information

1
Institute for Cardiovascular Regeneration, Centre of Molecular Medicine, Goethe University, Theodor Stern Kai 7, 60590 Frankfurt, Germany.
2
Institute for Neurology (Edinger Institute), Goethe University, 60528 Frankfurt, Germany.
3
Medizinische Klinik und Poliklinik I, Ludwig-Maximilians-University Munich, 81377 Munich, Germany.
4
ZIM III, Department of Cardiology, Goethe University, 60590 Frankfurt am Main, Germany.
5
Institute of Physiology and Pathophysiology, Division of Cardiovascular Physiology, 69120 Heidelberg, Germany.
6
German Center of Cardiovascular Research (DZHK), Partnersite Heidelberg, Mannheim, Germany.
7
German Center of Cardiovascular Research (DZHK), Partnersite Munich, Germany.
8
German Center of Cardiovascular Research (DZHK), Partnersite RheinMain, Germany.

Abstract

Aims:

Vessel maturation involves the recruitment of mural cells such as pericytes and smooth muscle cells. Laminar shear stress is a major trigger for vessel maturation, but the molecular mechanisms by which shear stress affects recruitment of pericytes are unclear. MicroRNAs (miRs) are small non-coding RNAs, which post-transcriptionally control gene expression. The aim of the present study was to unveil the mechanism by which shear stress-regulated microRNAs contribute to vessel maturation.

Methods and results:

Here, we show that laminar shear stress increased miR-27a and miR-27b expression in vitro and in ex vivo in mouse femoral artery explants. Overexpression of miR-27b in endothelial cells increased pericyte adhesion and pericyte recruitment in vitro. In vitro barrier function of endothelial-pericyte co-cultures was augmented by miR-27b overexpression, whereas inhibition of miR-27a/b reduced adhesion and pericyte coverage and decreased barrier functions. In vivo, pharmacological inhibition of miR-27a/b by locked nucleic acid antisense oligonucleotides significantly reduced pericyte coverage and increased water content in the murine uterus. MiR-27b overexpression repressed semaphorins (SEMA), which mediate repulsive signals, and the vessel destabilizing human but not mouse Angiopoietin-2 (Ang-2). Silencing of SEMA6A and SEMA6D rescued the reduced pericyte adhesion by miR-27 inhibition. Furthermore, inhibition of SEMA6D increased barrier function of an endothelial-pericyte co-culture in vitro.

Conclusion:

The present study demonstrates for the first time that shear stress-regulated miR-27b promotes the interaction of endothelial cells with pericytes, partly by repressing SEMA6A and SEMA6D.

KEYWORDS:

Endothelial cell; Laminar shear stress; MicroRNA; Pericyte; Semaphorins

PMID:
28453731
DOI:
10.1093/cvr/cvx032
[Indexed for MEDLINE]

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