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Fluid shear stress induced-endothelial phenotypic transition contributes to cerebral ischemia–reperfusion injury and repair
- Source :
- APL Bioengineering, Vol 8, Iss 1, Pp 016110-016110-19 (2024)
- Publication Year :
- 2024
- Publisher :
- AIP Publishing LLC, 2024.
-
Abstract
- Long-term ischemia leads to insufficient cerebral microvascular perfusion and dysfunction. Reperfusion restores physiological fluid shear stress (FSS) but leads to serious injury. The mechanism underlying FSS-induced endothelial injury in ischemia–reperfusion injury (IRI) remains poorly understood. In this study, a rat model of middle cerebral artery occlusion was constructed to explore cerebrovascular endothelial function and inflammation in vivo. Additionally, the rat brain microvascular endothelial cells (rBMECs) were exposed to a laminar FSS of 0.5 dyn/cm2 for 6 h and subsequently restored to physiological fluid shear stress level (2 dyn/cm2) for 2 and 12 h, respectively. We found that reperfusion induced endothelial-to-mesenchymal transition (EndMT) in endothelial cells, leading to serious blood–brain barrier dysfunction and endothelial inflammation, accompanied by the nuclear accumulation of Yes-associated protein (YAP). During the later stage of reperfusion, cerebral endothelium was restored to the endothelial phenotype with a distinct change in mesenchymal-to-endothelial transition (MEndT), while YAP was translocated and phosphorylated in the cytoplasm. Knockdown of YAP or inhibition of actin polymerization markedly impaired the EndMT in rBMECs. These findings suggest that ischemia–reperfusion increased intensity of FSS triggered an EndMT process and, thus, led to endothelial inflammation and tissue injury, whereas continuous FSS induced a time-dependent reversal MEndT event contributing to the endothelial repair. This study provides valuable insight for therapeutic strategies targeting IRI.
- Subjects :
- Biotechnology
TP248.13-248.65
Medical technology
R855-855.5
Subjects
Details
- Language :
- English
- ISSN :
- 24732877
- Volume :
- 8
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- APL Bioengineering
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.62461df978a24a658fc80f9d336ba0d2
- Document Type :
- article
- Full Text :
- https://doi.org/10.1063/5.0174825