Academic Journal
ICAM-1 targeted extracellular vesicles loaded with HC-070 mitigate vascular oxidative stress and inflammation in obstructive sleep apnea hypopnea syndrome by inhibiting TRPC5.
| Τίτλος: | ICAM-1 targeted extracellular vesicles loaded with HC-070 mitigate vascular oxidative stress and inflammation in obstructive sleep apnea hypopnea syndrome by inhibiting TRPC5. |
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| Συγγραφείς: | Zhang Y; Department of Respiratory and Critical Care Medicine, The Affiliated Yongchuan Hospital of Chongqing Medical University, Chongqing, 402160, China., Rong K; Department of Respiratory and Critical Care Medicine, The Affiliated Yongchuan Hospital of Chongqing Medical University, Chongqing, 402160, China., Zhang R; Department of Emergency, The Affiliated Yongchuan Hospital of Chongqing Medical University, Chongqing, 402160, China., Kuang J; Department of Neurology, The Affiliated Yongchuan Hospital of Chongqing Medical University, Chongqing, 402160, China., Zhang M; Department of Neurology, The Affiliated Yongchuan Hospital of Chongqing Medical University, Chongqing, 402160, China., Yu Y; Department of Emergency, The Affiliated Yongchuan Hospital of Chongqing Medical University, Chongqing, 402160, China. Electronic address: yuyichuan@hospital.cqmu.edu.cn., Yang Z; Department of Neurology, The Affiliated Yongchuan Hospital of Chongqing Medical University, Chongqing, 402160, China. Electronic address: yangzhao5140@sohu.com. |
| Πηγή: | Free radical biology & medicine [Free Radic Biol Med] 2026 Jul; Vol. 250, pp. 30-48. Date of Electronic Publication: 2026 Mar 13. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Science Country of Publication: United States NLM ID: 8709159 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4596 (Electronic) Linking ISSN: 08915849 NLM ISO Abbreviation: Free Radic Biol Med Subsets: MEDLINE |
| Imprint Name(s): | Publication: Tarrytown, NY : Elsevier Science Original Publication: New York : Pergamon, c1987- |
| Ιατρικοί όροι (MeSH): | Intercellular Adhesion Molecule-1*/metabolism , Intercellular Adhesion Molecule-1*/genetics , Sleep Apnea, Obstructive*/pathology , Sleep Apnea, Obstructive*/metabolism , Sleep Apnea, Obstructive*/drug therapy , Sleep Apnea, Obstructive*/genetics , Inflammation*/pathology , Inflammation*/metabolism , Inflammation*/drug therapy , TRPC Cation Channels*/antagonists & inhibitors , TRPC Cation Channels*/genetics , TRPC Cation Channels*/metabolism , Extracellular Vesicles*/metabolism, Oxidative Stress/drug effects ; Reactive Oxygen Species/metabolism ; Mesenchymal Stem Cells/metabolism ; Animals ; Humans ; Mice ; Human Umbilical Vein Endothelial Cells ; Male ; Disease Models, Animal |
| Περίληψη: | Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) significantly contributes to cardiovascular diseases through severe endothelial dysfunction, a pathology driven primarily by chronic intermittent hypoxia (CIH)-induced oxidative stress and inflammation. Current interventions inadequately address this vascular component. Human umbilical mesenchymal stem cell-derived extracellular vesicles (HUMSC-EVs) have regenerative potential, but improved targeting is needed to maximize therapeutic efficacy. This study sought to engineer and evaluate Intercellular Adhesion Molecule 1 (ICAM-1) targeted EVs loaded with the Transient Receptor Potential Channel C5 (TRPC5) inhibitor HC-070 (ICAM-1+H-EVs) for their ability to ameliorate oxidative damage in OSAHS. We employed a CIH mouse model and IH-treated HUVECs, and characterized ICAM-1+H-EVs using Western blotting and ExoView. ICAM-1+H-EVs significantly enhanced HUVEC uptake and, in both in vivo and in vitro settings, alleviated oxidative stress by lowering Reactive Oxygen Species (ROS) and Malondialdehyde (MDA) levels and restoring the activities of antioxidant enzymes Superoxide Dismutase (SOD) and Glutathione Peroxidase (GSH-PX). Furthermore, ICAM-1+H-EVs substantially suppressed inflammation by lowering TNF-α and IL-6 levels and mitigated mitochondrial ROS and morphological damage. This novel strategy targets TRPC5-mediated calcium influx, providing a potent therapeutic approach to interrupt the oxidative stress and inflammatory cycle driving OSAHS-associated vascular dysfunction. (Copyright © 2026 Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Extracellular vesicles; Intercellular adhesion molecule 1; Malondialdehyde; Obstructive sleep apnea hypopnea syndrome; Oxidative stress; TRPC5 |
| Substance Nomenclature: | 126547-89-5 (Intercellular Adhesion Molecule-1) 0 (TRPC Cation Channels) 0 (TRPC5 protein, human) 0 (Reactive Oxygen Species) 0 (ICAM1 protein, human) |
| Entry Date(s): | Date Created: 20260315 Date Completed: 20260710 Latest Revision: 20260710 |
| Update Code: | 20260711 |
| DOI: | 10.1016/j.freeradbiomed.2026.03.042 |
| PMID: | 41833586 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1873-4596 |
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| DOI: | 10.1016/j.freeradbiomed.2026.03.042 |