miRNA-6236 Regulation of Postischemic Skeletal Muscle Angiogenesis

Arul M Mani; Victor Lamin; Ronan C Peach; Eli H Friesen; Thomas Wong; Madhu V Singh; Ayotunde O Dokun

doi:10.1161/JAHA.124.035923

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miRNA-6236 Regulation of Postischemic Skeletal Muscle Angiogenesis

Journal article

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miRNA-6236 Regulation of Postischemic Skeletal Muscle Angiogenesis

Arul M Mani, Victor Lamin, Ronan C Peach, Eli H Friesen, Thomas Wong, Madhu V Singh and Ayotunde O Dokun

Journal of the American Heart Association, Vol.13(23), e035923

11/27/2024

DOI: 10.1161/JAHA.124.035923

PMCID: PMC11681604

PMID: 39604034

Appears in UI Libraries Support Open Access

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Abstract

Peripheral arterial disease affects >200 million people worldwide and is characterized by impaired blood flow to the lower extremities. There are no effective medical treatments available. Using the mouse hind-limb ischemia model and miRNA sequencing, we identified a novel miRNA, miR-6236, whose expression significantly elevated in ischemic mouse limbs compared with nonischemic limbs. The role of miR-6236 in general or in postischemic angiogenesis is not known. Here we describe its role using in vivo and in vitro models of peripheral arterial disease. In primary mouse and human endothelial cells, we studied the effect of simulated ischemia on miR-6236 expression and assessed its role in cell viability, apoptosis, migration, and tube formation during ischemia. Furthermore, we developed miR-6236 null mice and tested its role in postischemic perfusion recovery using the hind-limb ischemia model. Lastly, using bioinformatics and gene expression analysis, we identified putative angiogenic miR-6236 targets. In vitro simulated ischemia-enhanced miR-6236 expression in mouse and human endothelial cells, whereas its inhibition improved viability, migration, tube formation, and reduced apoptosis. In vivo ischemic mouse skeletal muscle tissue showed higher miR-6236 expression compared with nonischemic muscles. Loss of miR-6236 improved impaired postischemic perfusion recovery and poor angiogenesis associated with streptozotocin-induced diabetes in mice. Six of the 8 miR-6236 predicted angiogenic target mRNAs showed expression consistent with regulation by miR-6236 in ischemic skeletal muscle. Our results show for the first time that miR-6236 plays a key role in regulating postischemic perfusion recovery and angiogenesis.

Angiogenesis

Ischemia

endothelial cells

peripheral arterial disease

miR‐6236

UIOWA OA Agreement

Details

Title: Subtitle: miRNA-6236 Regulation of Postischemic Skeletal Muscle Angiogenesis
Creators: Arul M Mani - University of Iowa
Victor Lamin - University of Iowa
Ronan C Peach - University of Iowa
Eli H Friesen - University of Iowa
Thomas Wong - University of Iowa
Madhu V Singh - University of Iowa
Ayotunde O Dokun - University of Iowa
Resource Type: Journal article
Publication Details: Journal of the American Heart Association, Vol.13(23), e035923
DOI: 10.1161/JAHA.124.035923
PMID: 39604034
PMCID: PMC11681604
NLM abbreviation: J Am Heart Assoc
ISSN: 2047-9980
eISSN: 2047-9980
Publisher: Wiley
Grant note: National Heart, Lung, and Blood Institute: R01 HL130399 American Heart Association Career Development Award: 24CDA1271629
This work was supported by the National Heart, Lung, and Blood Institute (R01 HL130399 to A.O.D.). A.M.M. is supported by American Heart Association Career Development Award (award number: 24CDA1271629).
Language: English
Date published: 11/27/2024
Academic Unit: Molecular Physiology and Biophysics; Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984751760202771

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