Exposure of Endothelium to Biomimetic Flow Waveforms Yields Identification of miR-199a-5p as a Potent Regulator of Arteriogenesis

Molecular Therapy. Nucleic Acids
Joshua L HeusleinRichard J Price

Abstract

Arteriogenesis, the growth of endogenous collateral arteries bypassing arterial occlusion(s), is a fundamental shear stress-induced adaptation with implications for treating peripheral arterial disease (PAD). Nonetheless, endothelial mechano-signaling during arteriogenesis is incompletely understood. Here we tested the hypothesis that a mechanosensitive microRNA, miR-199a-5p, regulates perfusion recovery and collateral arteriogenesis following femoral arterial ligation (FAL) via control of monocyte recruitment and pro-arteriogenic gene expression. We have previously shown that collateral artery segments exhibit distinctly amplified arteriogenesis if they are exposed to reversed flow following FAL in the mouse. We performed a genome-wide analysis of endothelial cells exposed to a biomimetic reversed flow waveform. From this analysis, we identified mechanosensitive miR-199a-5p as a novel candidate regulator of collateral arteriogenesis. In vitro, miR-199a-5p inhibited pro-arteriogenic gene expression (IKKβ, Cav1) and monocyte adhesion to endothelium. In vivo, following FAL in mice, miR-199a-5p overexpression impaired foot perfusion and arteriogenesis. In contrast, a single intramuscular anti-miR-199a-5p injection elicited a robus...Continue Reading

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Citations

Jan 11, 2019·Cardiovascular Research·Joshua L HeusleinRichard J Price
Jun 27, 2019·International Journal of Molecular Sciences·Catherine M GorickRichard J Price
Jan 3, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Daniel Pérez-CremadesMark W Feinberg
Jun 11, 2021·Circulation Research·Brian H Annex, John P Cooke
Sep 28, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Neha S DoleTamara Alliston

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Datasets Mentioned

BETA
GSE46248

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BETA
confocal microscopy
transfection

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R script
Fiji Analyze Particles tool

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