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bioRxiv · 10.1101/2025.03.27.645845

MiR-126 Improves the Therapeutic Effect of EPC in Hypertensive Ischemic Stroke

Huang, J.·Zhao, B.·Li, X.·Ding, l.·Fu, M.·Song, Y.·Qu, M.·Chen, D.·Yang, G.-Y.·Gao, P.-J.
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Abstract

Background and PurposeHypertension promotes circulatory endothelial inflammation, reduces endothelial progenitor cell (EPC) function, and impairs their therapeutic potential following ischemic stroke. MiR-126 is known to regulate vascular development and angiogenesis. This study investigates the therapeutic potential of miR-126 by overexpressing it in EPCs to enhance their efficacy in hypertensive stroke conditions. MethodsAdult spontaneously hypertensive rats (SHRs, n=118) underwent permanent suture middle cerebral artery occlusion (MCAO) to induce ischemic stroke. One week post-stroke, animals were injected with EPCs overexpressing miR-126 or control EPCs. Treatment effects were evaluated over 35 days, using neurological scoring, infarct volume measurements, behavioral testing, and assessments of neuroinflammation, blood pressure, and angiogenesis. Exosomes from miR-126 overexpressing EPCs were isolated and analyzed for mechanistic studies. ResultsIn vitro, miR-126 enhanced EPC angiogenic function under stress. In vivo, miR-126 modified EPC treatment improved functional recovery, reduced infarct volume, and promoted angiogenesis compared to controls in SHRs. Furthermore, miR-126 treatment preserved the blood-brain barrier, reduced peripheral immune cell infiltration, and modulated neuroinflammation. Exosomes derived from miR-126 overexpression EPCs also promoted angiogenesis and reduced endothelial activation under stress conditions. ConclusionsEPC overexpressing miR-126 provides neuroprotection by enhancing angiogenesis, reducing ischemic injury, and preserving blood-brain barrier integrity in hypertensive stroke models. This approach modulates neuroinflammation and improves neurological outcomes, suggesting gene-modified EPCs as a promising strategy for ischemic stroke therapy, particularly under hypertensive conditions.

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Huang, J., Zhao, B., Li, X., Ding, l., Fu, M., Song, Y., Qu, M., Chen, D., Yang, G.-Y., Gao, P.-J.. 2025-04-01. MiR-126 Improves the Therapeutic Effect of EPC in Hypertensive Ischemic Stroke. https://doi.org/10.1101/2025.03.27.645845

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