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; Gertz, Karen

Loss of endothelial YAP/TAZ reduces the size of chronic stroke lesions and alters the endothelial environment

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Item Type:	Article
Title:	Loss of endothelial YAP/TAZ reduces the size of chronic stroke lesions and alters the endothelial environment
Creators Name:	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
Abstract:	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 to promote neuroprotection after stroke.
Keywords:	Endothelial Cells, Inflammation, Ischemic Stroke, Neuroprotection, YAP/TAZ, Animals, Mice
Source:	Journal of the American Heart Association
ISSN:	2047-9980
Publisher:	American Heart Association
Page Range:	e040079
Date:	26 November 2025
Official Publication:	https://doi.org/10.1161/jaha.124.040079
PubMed:	View item in PubMed

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