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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| Format: | Article |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Digital Health |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fdgth.2022.836579/full |
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| author | Neil Patel Deborah D. Chin Gregory A. Magee Eun Ji Chung Eun Ji Chung Eun Ji Chung Eun Ji Chung Eun Ji Chung Eun Ji Chung |
| author_facet | Neil Patel Deborah D. Chin Gregory A. Magee Eun Ji Chung Eun Ji Chung Eun Ji Chung Eun Ji Chung Eun Ji Chung Eun Ji Chung |
| author_sort | Neil Patel |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T14:01:29Z |
| format | Article |
| id | doaj.art-dbdcd0d2e2b748f2b088691ddae1eb18 |
| institution | Directory Open Access Journal |
| issn | 2673-253X |
| language | English |
| last_indexed | 2024-04-12T14:01:29Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Digital Health |
| spelling | doaj.art-dbdcd0d2e2b748f2b088691ddae1eb182022-12-22T03:30:11ZengFrontiers Media S.A.Frontiers in Digital Health2673-253X2022-06-01410.3389/fdgth.2022.836579836579Therapeutic Response of miR-145 Micelles on Patient-Derived Vascular Smooth Muscle CellsNeil Patel0Deborah D. Chin1Gregory A. Magee2Eun Ji Chung3Eun Ji Chung4Eun Ji Chung5Eun Ji Chung6Eun Ji Chung7Eun Ji Chung8Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, United StatesDepartment of Biomedical Engineering, University of Southern California, Los Angeles, CA, United StatesDivision of Vascular Surgery and Endovascular Therapy, Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesDepartment of Biomedical Engineering, University of Southern California, Los Angeles, CA, United StatesDivision of Vascular Surgery and Endovascular Therapy, Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesMork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA, United StatesDepartment of Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesDivision of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesDepartment of Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesDuring 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.https://www.frontiersin.org/articles/10.3389/fdgth.2022.836579/fullnanomedicinemiR-145personalized medicineplaquevascular smooth muscle cell |
| spellingShingle | Neil Patel Deborah D. Chin Gregory A. Magee Eun Ji Chung Eun Ji Chung Eun Ji Chung Eun Ji Chung Eun Ji Chung Eun Ji Chung Therapeutic Response of miR-145 Micelles on Patient-Derived Vascular Smooth Muscle Cells Frontiers in Digital Health nanomedicine miR-145 personalized medicine plaque vascular smooth muscle cell |
| 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 | nanomedicine miR-145 personalized medicine plaque vascular smooth muscle cell |
| url | https://www.frontiersin.org/articles/10.3389/fdgth.2022.836579/full |
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