Shear Stress-Induced miR-143-3p in Collateral Arteries Contributes to Outward Vessel Growth by Targeting Collagen V-α2

Kerstin Troidl, Thomas Hammerschick, Julian Albarran-Juarez, Georg Jung, Wilma Schierling, Sarah Tonack, Marcus Krüger, Benjamin Matuschke, Christian Troidl, Wolfgang Schaper, Thomas Schmitz-Rixen, Klaus T Preissner, Silvia Fischer

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

16 Citations (Scopus)

Abstract

OBJECTIVE: Arteriogenesis, describing the process of collateral artery growth, is activated by fluid shear stress (FSS). Since this vascular mechanotransduction may involve microRNAs (miRNAs), we investigated the FSS-induced expression of vascular cell miRNAs and their functional impact on collateral artery growth during arteriogenesis. Approach and Results: To this end, rats underwent femoral artery ligation and arteriovenous anastomosis to increase collateral blood flow to maximize FSS and trigger collateral vessel remodeling. Five days after surgery, a miRNA expression profile was obtained from collateral tissue, and upregulation of 4 miRNAs (miR-24-3p, miR-143-3p, miR-146a-5p, and miR-195-5p) was verified by quantitative polymerase chain reaction. Knockdown of miRNAs at the same time of the surgery in an in vivo mouse ligation and recovery model demonstrated that inhibition of miR-143-3p only severely impaired blood flow recovery due to decreased arteriogenesis. In situ hybridization revealed distinct localization of miR-143-3p in the vessel wall of growing collateral arteries predominantly in smooth muscle cells. To investigate the mechanotransduction of FSS leading to the increased miR-143-3p expression, cultured endothelial cells were exposed to FSS. This provoked the expression and release of TGF-β (transforming growth factor-β), which increased the expression of miR-143-3p in smooth muscle cells in the presence of SRF (serum response factor) and myocardin. COL5A2 (collagen type V-α2)-a target gene of miR-143-3p predicted by in silico analysis-was found to be downregulated in growing collaterals.

CONCLUSIONS: These results indicate that the increased miR-143-3p expression in response to FSS might contribute to the reorganization of the extracellular matrix, which is important for vascular remodeling processes, by inhibiting collagen V-α2 biosynthesis.

Original languageEnglish
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume40
Issue5
Pages (from-to)e126-e137
Number of pages10
ISSN1079-5642
DOIs
Publication statusPublished - May 2020

Keywords

  • arteriogenesis
  • collagen type V-α2
  • collateral growth
  • fluid shear stress
  • miR-143
  • microRNA

Fingerprint

Dive into the research topics of 'Shear Stress-Induced miR-143-3p in Collateral Arteries Contributes to Outward Vessel Growth by Targeting Collagen V-α2'. Together they form a unique fingerprint.

Cite this