{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:47:56Z","timestamp":1785415676896,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,7]]},"group-title":"Immunology","reference-count":78,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["RO1 HL138931"],"award-info":[{"award-number":["RO1 HL138931"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["RO1 HL153341"],"award-info":[{"award-number":["RO1 HL153341"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32 HL160491"],"award-info":[{"award-number":["T32 HL160491"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["L30 HL175742"],"award-info":[{"award-number":["L30 HL175742"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Abdominal aortic aneurysms (AAA) are characterized by dilation of the aorta that can lead to aortic rupture and death. The transcriptional co-activators Yes-Associated Protein (YAP) and WW-domain-containing transcriptional co-activator with PDZ-binding motif (TAZ) are mechanosensitive effectors of the highly conserved Hippo signaling pathway. It is hypothesized that cell-specific YAP\/TAZ signaling in endothelial cells (EC) plays a pivotal role in mediating AAA formation and rupture.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    Single-cell RNA-sequencing in human AAAs was performed and differentially expressed genes (DEGs) were identified in the endothelial cell cluster. YAP\/TAZ mRNA and protein expression were also assessed in human AAA and control aortic tissue. Two established murine AAA models were used with male C57BL\/6 and\n                    <jats:italic>\n                      EC-CreER\n                      <jats:sup>T<\/jats:sup>\n                    <\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    <jats:italic>\n                      -YAP\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      \/TAZ\n                      <jats:sup>fl\/fl<\/jats:sup>\n                    <\/jats:italic>\n                    mice with\/without Verteporfin (VPF, YAP\/TAZ inhibitor) and XMU-MP-1 (YAP\/TAZ activator) treatments. On postoperative days 14 and 28, aortic diameter, histology, cytokine, and MMP2 expressions were evaluated.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    A significant alteration in EC-specific differentially expressed YAP\/TAZ-related genes was observed in which 242 genes were upregulated and 71 genes were downregulated in AAA compared to controls. Human AAA tissue showed a significant increase in YAP and TAZ protein expressions compared to controls. Elastase-treated EC-YAP\/TAZ\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice showed a significant decrease in AAA diameter compared to littermate controls. Histological quantification revealed preservation of \u03b1-smooth muscle actin, reduced elastin fiber breaks, and decreased macrophage infiltration in EC-YAP\/TAZ\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice compared to littermate controls. Importantly, pharmacological inhibition of YAP\/TAZ using VPF significantly attenuated AAAs in two experimental murine models.\n                    <jats:italic>In vitro<\/jats:italic>\n                    data demonstrates that VPF inhibits endothelial cell YAP expression, downregulating pathways associated with pathogenic angiogenesis and vascular inflammation.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These data suggest that EC-specific YAP\/TAZ signaling mediates AAA formation. Pharmacological inhibition of the Hippo pathway can significantly mitigate aortic inflammation and vascular remodeling to decrease the progression of AAAs and prevent aortic rupture.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>Expression of YAP\/TAZ in endothelial cells is dysregulated in human AAAs.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        Experimental murine models demonstrate that:\n                        <jats:italic>a)<\/jats:italic>\n                        endothelial-cell specific deletion of YAP\/TAZ protects against AAA formation, and pharmacologic alteration with\n                        <jats:italic>b)<\/jats:italic>\n                        verteporfin attenuates AAA formation, and\n                        <jats:italic>c)<\/jats:italic>\n                        XMU-MP-1 significantly exacerbates aortic inflammation, vascular remodeling, and rupture.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Verteporfin inhibits endothelial YAP\/TAZ activation by modulating ECM remodeling, pathogenic angiogenesis, pro-inflammatory cytokine and chemokine expression.<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.64898\/2026.07.01.735919","type":"posted-content","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T22:00:11Z","timestamp":1783461611000},"source":"Crossref","is-referenced-by-count":0,"title":["YAP\/TAZ Signaling in Endothelial Cells Mediates the Pathogenesis of Abdominal Aortic Aneurysm Formation"],"prefix":"10.64898","author":[{"given":"Walker 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