MicroRNA-146a regulates perfusion recovery in response to arterial occlusion via arteriogenesis

Joshua L. Heuslein, Stephanie P. McDonnell, Ji Song, Brian H. Annex, Richard J. Price

Research output: Contribution to journalArticle

Abstract

The growth of endogenous collateral arteries that bypass arterial occlusion(s), or arteriogenesis, is a fundamental shear stress-induced adaptation with implications for treating peripheral arterial disease. MicroRNAs (miRs) are key regulators of gene expression in response to injury and have strong therapeutic potential. In a previous study, we identified miR-146a as a candidate regulator of vascular remodeling. Here, we tested whether miR-146a regulates in vitro angiogenic endothelial cell (EC) behaviors, as well as perfusion recovery, arteriogenesis, and angiogenesis in response to femoral arterial ligation (FAL) in vivo. We found miR-146a inhibition impaired EC tube formation and migration in vitro. Following FAL, Balb/c mice were treated with a single, intramuscular injection of anti-miR-146a or scramble locked nucleic acid (LNA) oligonucleotides directly into the non-ischemic gracilis muscles. Serial laser Doppler imaging demonstrated that anti-miR-146a treated mice exhibited significantly greater perfusion recovery (a 16% increase) compared mice treated with scramble LNA. Moreover, anti-miR-146a treated mice exhibited a 22% increase in collateral artery diameter compared to controls, while there was no significant effect on in vivo angiogenesis or muscle regeneration. Despite exerting no beneficial effects on angiogenesis, the inhibition of mechanosensitive miR-146a enhances perfusion recovery after FAL via enhanced arteriogenesis.

Original languageEnglish (US)
Article number1
JournalFrontiers in Bioengineering and Biotechnology
Volume6
Issue numberJAN
DOIs
StatePublished - Jan 22 2018
Externally publishedYes

Fingerprint

Thigh
MicroRNAs
Ligation
Perfusion
Nucleic acids
Endothelial cells
Recovery
Muscle
Endothelial Cells
Arteries
Oligonucleotides
Peripheral Arterial Disease
Intramuscular Injections
Regulator Genes
Gene expression
Shear stress
Regeneration
Lasers
Gene Expression
Imaging techniques

Keywords

  • Angiogenesis
  • Arteriogenesis
  • Endothelial cell
  • Epigenetics
  • Hindlimb ischemia
  • MicroRNA
  • Peripheral arterial disease
  • Shear stress

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Histology
  • Biomedical Engineering

Cite this

MicroRNA-146a regulates perfusion recovery in response to arterial occlusion via arteriogenesis. / Heuslein, Joshua L.; McDonnell, Stephanie P.; Song, Ji; Annex, Brian H.; Price, Richard J.

In: Frontiers in Bioengineering and Biotechnology, Vol. 6, No. JAN, 1, 22.01.2018.

Research output: Contribution to journalArticle

Heuslein, Joshua L. ; McDonnell, Stephanie P. ; Song, Ji ; Annex, Brian H. ; Price, Richard J. / MicroRNA-146a regulates perfusion recovery in response to arterial occlusion via arteriogenesis. In: Frontiers in Bioengineering and Biotechnology. 2018 ; Vol. 6, No. JAN.
@article{2a24320a14a9497c9a091fb4cc2324dd,
title = "MicroRNA-146a regulates perfusion recovery in response to arterial occlusion via arteriogenesis",
abstract = "The growth of endogenous collateral arteries that bypass arterial occlusion(s), or arteriogenesis, is a fundamental shear stress-induced adaptation with implications for treating peripheral arterial disease. MicroRNAs (miRs) are key regulators of gene expression in response to injury and have strong therapeutic potential. In a previous study, we identified miR-146a as a candidate regulator of vascular remodeling. Here, we tested whether miR-146a regulates in vitro angiogenic endothelial cell (EC) behaviors, as well as perfusion recovery, arteriogenesis, and angiogenesis in response to femoral arterial ligation (FAL) in vivo. We found miR-146a inhibition impaired EC tube formation and migration in vitro. Following FAL, Balb/c mice were treated with a single, intramuscular injection of anti-miR-146a or scramble locked nucleic acid (LNA) oligonucleotides directly into the non-ischemic gracilis muscles. Serial laser Doppler imaging demonstrated that anti-miR-146a treated mice exhibited significantly greater perfusion recovery (a 16{\%} increase) compared mice treated with scramble LNA. Moreover, anti-miR-146a treated mice exhibited a 22{\%} increase in collateral artery diameter compared to controls, while there was no significant effect on in vivo angiogenesis or muscle regeneration. Despite exerting no beneficial effects on angiogenesis, the inhibition of mechanosensitive miR-146a enhances perfusion recovery after FAL via enhanced arteriogenesis.",
keywords = "Angiogenesis, Arteriogenesis, Endothelial cell, Epigenetics, Hindlimb ischemia, MicroRNA, Peripheral arterial disease, Shear stress",
author = "Heuslein, {Joshua L.} and McDonnell, {Stephanie P.} and Ji Song and Annex, {Brian H.} and Price, {Richard J.}",
year = "2018",
month = "1",
day = "22",
doi = "10.3389/fbioe.2018.00001",
language = "English (US)",
volume = "6",
journal = "Frontiers in Bioengineering and Biotechnology",
issn = "2296-4185",
publisher = "Frontiers Media S. A.",
number = "JAN",

}

TY - JOUR

T1 - MicroRNA-146a regulates perfusion recovery in response to arterial occlusion via arteriogenesis

AU - Heuslein, Joshua L.

AU - McDonnell, Stephanie P.

AU - Song, Ji

AU - Annex, Brian H.

AU - Price, Richard J.

PY - 2018/1/22

Y1 - 2018/1/22

N2 - The growth of endogenous collateral arteries that bypass arterial occlusion(s), or arteriogenesis, is a fundamental shear stress-induced adaptation with implications for treating peripheral arterial disease. MicroRNAs (miRs) are key regulators of gene expression in response to injury and have strong therapeutic potential. In a previous study, we identified miR-146a as a candidate regulator of vascular remodeling. Here, we tested whether miR-146a regulates in vitro angiogenic endothelial cell (EC) behaviors, as well as perfusion recovery, arteriogenesis, and angiogenesis in response to femoral arterial ligation (FAL) in vivo. We found miR-146a inhibition impaired EC tube formation and migration in vitro. Following FAL, Balb/c mice were treated with a single, intramuscular injection of anti-miR-146a or scramble locked nucleic acid (LNA) oligonucleotides directly into the non-ischemic gracilis muscles. Serial laser Doppler imaging demonstrated that anti-miR-146a treated mice exhibited significantly greater perfusion recovery (a 16% increase) compared mice treated with scramble LNA. Moreover, anti-miR-146a treated mice exhibited a 22% increase in collateral artery diameter compared to controls, while there was no significant effect on in vivo angiogenesis or muscle regeneration. Despite exerting no beneficial effects on angiogenesis, the inhibition of mechanosensitive miR-146a enhances perfusion recovery after FAL via enhanced arteriogenesis.

AB - The growth of endogenous collateral arteries that bypass arterial occlusion(s), or arteriogenesis, is a fundamental shear stress-induced adaptation with implications for treating peripheral arterial disease. MicroRNAs (miRs) are key regulators of gene expression in response to injury and have strong therapeutic potential. In a previous study, we identified miR-146a as a candidate regulator of vascular remodeling. Here, we tested whether miR-146a regulates in vitro angiogenic endothelial cell (EC) behaviors, as well as perfusion recovery, arteriogenesis, and angiogenesis in response to femoral arterial ligation (FAL) in vivo. We found miR-146a inhibition impaired EC tube formation and migration in vitro. Following FAL, Balb/c mice were treated with a single, intramuscular injection of anti-miR-146a or scramble locked nucleic acid (LNA) oligonucleotides directly into the non-ischemic gracilis muscles. Serial laser Doppler imaging demonstrated that anti-miR-146a treated mice exhibited significantly greater perfusion recovery (a 16% increase) compared mice treated with scramble LNA. Moreover, anti-miR-146a treated mice exhibited a 22% increase in collateral artery diameter compared to controls, while there was no significant effect on in vivo angiogenesis or muscle regeneration. Despite exerting no beneficial effects on angiogenesis, the inhibition of mechanosensitive miR-146a enhances perfusion recovery after FAL via enhanced arteriogenesis.

KW - Angiogenesis

KW - Arteriogenesis

KW - Endothelial cell

KW - Epigenetics

KW - Hindlimb ischemia

KW - MicroRNA

KW - Peripheral arterial disease

KW - Shear stress

UR - http://www.scopus.com/inward/record.url?scp=85041313888&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041313888&partnerID=8YFLogxK

U2 - 10.3389/fbioe.2018.00001

DO - 10.3389/fbioe.2018.00001

M3 - Article

AN - SCOPUS:85041313888

VL - 6

JO - Frontiers in Bioengineering and Biotechnology

JF - Frontiers in Bioengineering and Biotechnology

SN - 2296-4185

IS - JAN

M1 - 1

ER -