| Title: | COPD airway epithelial cells-derived extracellular vesicles contribute to endothelial dysfunction and atherosclerosis via the miR-141-3p/PDCD4 axis |
| Journal: | Journal of Nanobiotechnology |
| Published: | 6 Feb 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41652466/ |
| DOI: | https://doi.org/10.1186/s12951-026-04091-0 |
Publication 18349
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Abstract
BackgroundChronic obstructive pulmonary disease (COPD) frequently coexists with extrapulmonary comorbidities, most notably cardiovascular diseases (CVD). However, the mechanisms linking COPD to CVD, particularly atherosclerotic CVD, remain poorly understood. Extracellular vesicles (EVs), as key mediators of inter-organ communication, may participate in this pathological connection. This study aims to determine whether EVs derived from airway epithelial cells (AECs) of individuals with COPD contribute to endothelial dysfunction and atherosclerosis.MethodsEVs were isolated from primary airway epithelial cells of COPD patients and matched controls. Their effects on endothelial cell function were assessed in vitro by evaluating inflammation, apoptosis, and monocyte adhesion. ApoE-/- mice were intravenously injected with these EVs to examine their impact on atherosclerotic lesion development. Differentially expressed microRNAs were identified, and the regulatory relationship between miR-141-3p and PDCD4 was validated through molecular assays. Additionally, miR-141-3p supplementation was performed to determine its therapeutic potential in mitigating endothelial injury and atherosclerosis.ResultsCOPD AECs-derived EVs markedly increased endothelial inflammation, apoptosis, and monocyte adhesion compared with control EVs. In ApoE-/- mice, COPD-derived EVs accelerated the formation of atherosclerotic plaques. Mechanistic analyses revealed that miR-141-3p was significantly downregulated in COPD EVs and directly targeted the 3' untranslated region of PDCD4 to regulate its transcription, leading to dysregulation of PDCD4/NF-κB signaling in endothelial cells. Restoration of miR-141-3p levels in COPD-derived EVs alleviated endothelial injury and reduced atherosclerotic lesion progression both in vitro and in vivo.ConclusionsThis study identifies a previously unrecognized mechanism by which COPD AECs-derived EVs may promote atherosclerotic CVD via miR-141-3p-mediated regulation of PDCD4 and subsequent activation of NF-κB signaling. These findings highlight miR-141-3p as a promising therapeutic target to reduce vascular complications in COPD.Graphical Abstract</p>
16 Keywords
- Animals
- Apoptosis
- Apoptosis Regulatory Proteins
- Atherosclerosis
- Endothelial Cells
- Epithelial Cells
- Extracellular Vesicles
- Female
- Humans
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout, ApoE
- MicroRNAs
- Pulmonary Disease, Chronic Obstructive
- RNA-Binding Proteins
10 Authors
- Zihan Wang
- Jun Shi
- Ying Liang
- Danyang Li
- Ying Luo
- Yue Zhang
- Yahong Chen
- Nan Li
- Xiaoyan Gai
- Yongchang Sun
1 Application
| Application ID | Title |
|---|---|
| 106707 | Causal effects of environmental, lifestyle, and genetic factors on chronic diseases. |
Enabling scientific discoveries that improve human health