Academic Journal
Loss of endothelial YAP/TAZ reduces the size of chronic stroke lesions and alters the endothelial environment
| Τίτλος: | Loss of endothelial YAP/TAZ reduces the size of chronic stroke lesions and alters the endothelial environment |
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| Συγγραφείς: | Göttert, Ria, Kikhia, Majed, Herzog, Marie-Louise, Pan, Wen, Klaus-Bergmann, Alexandra, Weiner, January, Beule, Dieter, Knauss, Samuel, Kronenberg, Golo, Bader, Michael, Gerhardt, Holger, Endres, Matthias, Gertz, Karen |
| Στοιχεία εκδότη: | American Heart Association |
| Έτος έκδοσης: | 2026 |
| Συλλογή: | Max-Delbrueck-Center for Molecular Medicine, Berlin: MDC Repository |
| Θεματικοί όροι: | Cardiovascular and Metabolic Diseases, Topic 3: Integrative Biomedicine |
| Περιγραφή: | BACKGROUND: Ischemic stroke remains a leading cause of morbidity and mortality worldwide, with limited treatment options available. Vascular dysfunction is a key pathomechanism, and brain endothelial cells (bECs) play a critical role in determining stroke outcomes. This study investigates the specific roles of YAP (yes-associated protein 1) and TAZ (WW domain containing transcription regulator 1) in regulating bEC functions during stroke. METHODS: Mice underwent 30-minute middle cerebral artery occlusion (MCAo) followed by reperfusion to model ischemic stroke. TAZ reporter mice were used to track stroke-induced subcellular changes in TAZ expression. Tamoxifen-inducible endothelial-specific Yap/Taz knockout and control mice were used to study YAP/TAZ's role in bEC function post-stroke. Stroke outcomes were measured by magnetic resonance imaging and NeuN (neuronal nuclei)-associated lesion analysis. Properties of bECs were assessed via immunohistochemistry and RNA sequencing. Inflammatory parameters were analyzed by flow cytometry of brain immune cells and quantitative polymerase chain reaction. RESULTS: Middle cerebral artery occlusion/reperfusion regulated Yap, Taz, and YAP/TAZ target gene expression in the brain. TAZ reporter mice confirmed stroke-induced endothelial YAP/TAZ activation. Endothelial-specific loss of YAP/TAZ reduced infarct volumes at 4 weeks after MCAo without impairing stroke-induced angiogenesis, revealing an unexpected neuroprotective role for endothelial YAP/TAZ depletion. YAP/TAZ deficiency modulated cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) and Wnt (wingless-related integration site) signaling genes in bECs and promoted myeloid cell recruitment and an anti-inflammatory vascular environment during the subacute phase of stroke. CONCLUSIONS: Our data suggest that endothelial YAP/TAZ affects the inflammatory milieu subacutely after ischemia and thereby influences the chronic course of stroke. Modulation of YAP/TAZ activity in ECs may be a promising therapeutic target ... |
| Τύπος εγγράφου: | article in journal/newspaper |
| Περιγραφή αρχείου: | application/pdf; other |
| Γλώσσα: | English |
| Relation: | https://edoc.mdc-berlin.de/id/eprint/25942/1/25942oa.pdf; https://edoc.mdc-berlin.de/id/eprint/25942/2/25942suppl.zip; Loss of endothelial YAP/TAZ reduces the size of chronic stroke lesions and alters the endothelial environment. Göttert, Ria, Kikhia, Majed, Herzog, Marie-Louise, Pan, Wen, Klaus-Bergmann, Alexandra, Weiner, January, Beule, Dieter, Knauss, Samuel, Kronenberg, Golo, Bader, Michael, Gerhardt, Holger, Endres, Matthias and Gertz, Karen Journal of the American Heart Association 15 (6): e040079. 17 March 2026; PMID:41294142; https://doi.org/10.1161/jaha.124.040079 |
| DOI: | 10.1161/jaha.124.040079 |
| Διαθεσιμότητα: | https://edoc.mdc-berlin.de/id/eprint/25942/ https://edoc.mdc-berlin.de/25942/ https://doi.org/10.1161/jaha.124.040079 |
| Rights: | cc_by_4 |
| Αριθμός Καταχώρησης: | edsbas.AC8C8C93 |
| Βάση Δεδομένων: | BASE |
| DOI: | 10.1161/jaha.124.040079 |
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