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Therapeutic Response of miR-145 Micelles on Patient-Derived Vascular Smooth Muscle Cells

During atherosclerosis, vascular smooth muscle cells (VSMCs) undergo a phenotypic transition from a healthy contractile state into pathological phenotypes including a proliferative and migratory, synthetic phenotype and osteochondrogenic-like phenotype that exacerbate plaques. Thus, inhibiting the t...

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Autores principales: Patel, Neil, Chin, Deborah D., Magee, Gregory A., Chung, Eun Ji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9240309/
https://www.ncbi.nlm.nih.gov/pubmed/35783597
http://dx.doi.org/10.3389/fdgth.2022.836579
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author Patel, Neil
Chin, Deborah D.
Magee, Gregory A.
Chung, Eun Ji
author_facet Patel, Neil
Chin, Deborah D.
Magee, Gregory A.
Chung, Eun Ji
author_sort Patel, Neil
collection PubMed
description During atherosclerosis, vascular smooth muscle cells (VSMCs) undergo a phenotypic transition from a healthy contractile state into pathological phenotypes including a proliferative and migratory, synthetic phenotype and osteochondrogenic-like phenotype that exacerbate plaques. Thus, inhibiting the transition of healthy, quiescent VSMCs to atherogenic cell types has the potential to mitigate atherosclerosis. To that end, previously, we reported that delivery of microRNA-145 (miR-145, a potent gatekeeper of the contractile VSMC phenotype) using nanoparticle micelles limited atherosclerotic plaque growth in murine models of atherosclerosis. Building on this preclinical data and toward clinical application, in this study, we tested the therapeutic viability of miR-145 micelles on patient-derived VSMCs and evaluated their effects based on disease severity. We collected vascular tissues from 11 patients with healthy, moderate, or severe stages of atherosclerosis that were discarded following vascular surgery or organ transplant, and isolated VSMCs from these tissues. We found that with increasing disease severity, patient-derived VSMCs had decreasing levels of contractile markers (miR-145, ACTA2, MYH11) and increasing levels of synthetic markers (KLF4, KLF5, and ELK1). Treatment with miR-145 micelles showed that an increase in disease severity correlated with a more robust response to therapy in VSMCs. Notably, miR-145 micelle therapy rescued contractile marker expression to baseline contractile levels in VSMCs derived from the most severely diseased tissues. As such, we demonstrate the use of miR-145 micelles across different stages of atherosclerosis disease and present further evidence of the translatability of miR-145 micelle treatment for atherosclerosis.
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spelling pubmed-92403092022-06-30 Therapeutic Response of miR-145 Micelles on Patient-Derived Vascular Smooth Muscle Cells Patel, Neil Chin, Deborah D. Magee, Gregory A. Chung, Eun Ji Front Digit Health Digital Health During atherosclerosis, vascular smooth muscle cells (VSMCs) undergo a phenotypic transition from a healthy contractile state into pathological phenotypes including a proliferative and migratory, synthetic phenotype and osteochondrogenic-like phenotype that exacerbate plaques. Thus, inhibiting the transition of healthy, quiescent VSMCs to atherogenic cell types has the potential to mitigate atherosclerosis. To that end, previously, we reported that delivery of microRNA-145 (miR-145, a potent gatekeeper of the contractile VSMC phenotype) using nanoparticle micelles limited atherosclerotic plaque growth in murine models of atherosclerosis. Building on this preclinical data and toward clinical application, in this study, we tested the therapeutic viability of miR-145 micelles on patient-derived VSMCs and evaluated their effects based on disease severity. We collected vascular tissues from 11 patients with healthy, moderate, or severe stages of atherosclerosis that were discarded following vascular surgery or organ transplant, and isolated VSMCs from these tissues. We found that with increasing disease severity, patient-derived VSMCs had decreasing levels of contractile markers (miR-145, ACTA2, MYH11) and increasing levels of synthetic markers (KLF4, KLF5, and ELK1). Treatment with miR-145 micelles showed that an increase in disease severity correlated with a more robust response to therapy in VSMCs. Notably, miR-145 micelle therapy rescued contractile marker expression to baseline contractile levels in VSMCs derived from the most severely diseased tissues. As such, we demonstrate the use of miR-145 micelles across different stages of atherosclerosis disease and present further evidence of the translatability of miR-145 micelle treatment for atherosclerosis. Frontiers Media S.A. 2022-06-15 /pmc/articles/PMC9240309/ /pubmed/35783597 http://dx.doi.org/10.3389/fdgth.2022.836579 Text en Copyright © 2022 Patel, Chin, Magee and Chung. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Digital Health
Patel, Neil
Chin, Deborah D.
Magee, Gregory A.
Chung, Eun Ji
Therapeutic Response of miR-145 Micelles on Patient-Derived Vascular Smooth Muscle Cells
title Therapeutic Response of miR-145 Micelles on Patient-Derived Vascular Smooth Muscle Cells
title_full Therapeutic Response of miR-145 Micelles on Patient-Derived Vascular Smooth Muscle Cells
title_fullStr Therapeutic Response of miR-145 Micelles on Patient-Derived Vascular Smooth Muscle Cells
title_full_unstemmed Therapeutic Response of miR-145 Micelles on Patient-Derived Vascular Smooth Muscle Cells
title_short Therapeutic Response of miR-145 Micelles on Patient-Derived Vascular Smooth Muscle Cells
title_sort therapeutic response of mir-145 micelles on patient-derived vascular smooth muscle cells
topic Digital Health
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9240309/
https://www.ncbi.nlm.nih.gov/pubmed/35783597
http://dx.doi.org/10.3389/fdgth.2022.836579
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