Platelet-derived microvesicles deliver miR-30e and promote VSMC apoptosis after balloon injury
| Autor: | Zonglai Jiang, Fei Zhuang, Han Bao, Zi-Tong Li, Ying-Xin Qi, Qing-Ping Yao, Yuan-Xiu Chen, Ji-Ting Liu, Hai-Peng Li |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
business.industry
RUNX2 Biomedical Engineering Medicine (miscellaneous) Apoptosis Platelet-derived microvesicles musculoskeletal system Balloon injury Microvesicles Computer Science Applications Intimal injury VSMC apoptosis miR-30e Vascular smooth muscle cells Medical technology Cancer research Medicine Platelet R855-855.5 business |
| Zdroj: | Medicine in Novel Technology and Devices, Vol 13, Iss, Pp 100103-(2022) |
| ISSN: | 2590-0935 |
| DOI: | 10.1016/j.medntd.2021.100103 |
| Popis: | During vascular remodeling after intimal injury, circulating platelets are activated by exposed collagen and release platelet-derived microvesicles (PMVs), which may contribute to the injury-induced apoptosis of vascular smooth muscle cells (VSMCs). However, the mechanisms in this process are still unclear. Using a rat balloon injury model, platelet adhesion at the injured site was detected, and promoted medial VSMC apoptosis was revealed with dT-mediated dUTP nick-end labeling (TUNEL) in vivo. VSMC apoptosis was promoted by coincubation with PMVs in vitro. Transcriptomics analysis indicated the abound expression of the microRNA-30 (miR-30) family in platelets, and the expression of the miR-30 family in platelets and PMVs was confirmed with qPCR. Ingenuity Pathway Analysis (IPA) software identified transcription factor 2 (RUNX2) as a pivotal molecule linking miR-30 and cellular apoptosis. In vitro, PMVs delivered miR-30e, an important member of the miR-30 family, into VSMCs and increased cell apoptosis. A dual-luciferase assay was adopted to verify the interaction of miR-30e with RUNX2, and fluorescence in situ hybridization (FISH) proved the cytoplasmic localization of miR-30e in VSMCs. The apoptotic effect on VSMCs was further confirmed by using miR-30e mimics and RUNX2 siRNA. Furthermore, RUNX2 siRNA altered the expression of its downstream genes, Tnfrsf11b, Smad6 and Mmp13, which may participate in apoptosis, as suggested by IPA. Our results indicated that PMVs play important roles in the interactions between circulating elements and VSMCs by delivering miR-30e to VSMCs and then promoting apoptosis. PMVs and potential intercellular messages may be novel therapeutic targets for preventing pathological vascular remodeling after intimal injury. |
| Databáze: | OpenAIRE |
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