{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:36:38Z","timestamp":1791999398001,"version":"4.4.0"},"reference-count":80,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2025,9,2]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>\n                      Hereditary hemorrhagic telangiectasia is an inherited vascular disorder characterized by arteriovenous malformations (AVMs). Loss-of-function variations in activin receptor-like kinase 1 (\n                      <jats:italic toggle=\"yes\">ALK1<\/jats:italic>\n                      ) cause type 2 hereditary hemorrhagic telangiectasia, and\n                      <jats:italic toggle=\"yes\">Alk1<\/jats:italic>\n                      knockout mice develop AVMs, along with overactivation of vascular endothelial growth factor receptor 2\/phosphoinositide 3-kinase\/AKT signaling. The full spectrum of signaling alterations resulting from\n                      <jats:italic toggle=\"yes\">ALK1<\/jats:italic>\n                      variations remains unknown, and more effective and specific inhibitors to combat AVM formation in patients are needed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      Single-cell RNA sequencing of endothelial-specific\n                      <jats:italic toggle=\"yes\">Alk1<\/jats:italic>\n                      knockout mouse retinas and controls was performed. Overexpression of fluid shear stress signaling signatures including the mechanosensitive ion channel PIEZO1 was confirmed in mouse and human type 2 hereditary hemorrhagic telangiectasia lesions. Genetic and pharmacological PIEZO1 inhibition was tested in\n                      <jats:italic toggle=\"yes\">Alk1<\/jats:italic>\n                      knockout mice, along with downstream PIEZO1 signaling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      A cluster of\n                      <jats:italic toggle=\"yes\">Alk1<\/jats:italic>\n                      mutant endothelial cells with altered arterio-venous identity overexpressed pathways related to fluid shear stress, hypoxia, inflammation, cell cycle, and vascular endothelial growth factor receptor 2\/phosphoinositide 3-kinase\/AKT signaling.\n                      <jats:italic toggle=\"yes\">Piezo1<\/jats:italic>\n                      deletion and pharmacological inhibition in\n                      <jats:italic toggle=\"yes\">Alk1<\/jats:italic>\n                      -deficient mice mitigated AVM formation, whereas\n                      <jats:italic toggle=\"yes\">Piezo1<\/jats:italic>\n                      overexpression enhanced AVM formation induced by ALK1 ligand blockade. Mechanistically, PIEZO1 inhibition reduced elevated vascular endothelial growth factor receptor 2\/AKT, ERK5-p62-KLF4, endothelial nitric oxide synthase, hypoxia, proliferation, and inflammation in ALK1-deficient endothelium.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>PIEZO1 expression and signaling are elevated in type 2 hereditary hemorrhagic telangiectasia. PIEZO1 blockade reduces AVM formation and alleviates cellular and molecular hallmarks of ALK1-deficient cells. This finding provides new insights into the mechanistic underpinnings of ALK1-related vascular diseases and identifies potential therapeutic targets to prevent AVMs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.124.073630","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T09:00:26Z","timestamp":1752656426000},"page":"599-615","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["PIEZO1 Overexpression in Hereditary Hemorrhagic Telangiectasia Arteriovenous Malformations"],"prefix":"10.1161","volume":"152","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3671-8618","authenticated-orcid":true,"given":"Hyojin","family":"Park","sequence":"first","affiliation":[{"name":"Cardiovascular Research Center, Department of Internal Medicine (H.P., S.L., J.F., M.A.S., L.H.Y., A.E.), Yale University School of Medicine, New Haven, CT."},{"name":"Department of Cellular and Molecular Physiology (H.P., J.F., A.E.), Yale University School of Medicine, New Haven, CT."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungwoon","family":"Lee","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center, Department of Internal Medicine (H.P., S.L., J.F., M.A.S., L.H.Y., A.E.), Yale University School of Medicine, New Haven, CT."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Furtado","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center, Department of Internal Medicine (H.P., S.L., J.F., M.A.S., L.H.Y., A.E.), Yale University School of Medicine, New Haven, CT."},{"name":"Department of Cellular and Molecular Physiology (H.P., J.F., A.E.), Yale University School of Medicine, New Haven, CT."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2363-6047","authenticated-orcid":true,"given":"Mark","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Hematology and Medical Oncology (M.R., L.H.Y.), Yale University School of Medicine, New Haven, CT."},{"name":"Center of Molecular and Cellular Oncology (M.R.), Yale University School of Medicine, New Haven, CT."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8557-5986","authenticated-orcid":true,"given":"Richard J.","family":"Antaya","sequence":"additional","affiliation":[{"name":"Departments of Dermatology, Pediatrics, and Nursing (R.J.A.), Yale University School of Medicine, New Haven, CT."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3833-0342","authenticated-orcid":true,"given":"S. Paul","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience, Barrow Aneurysm &amp; AVM Research Center, Barrow Neurological Institute, Phoenix, AZ (S.P.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8245-875X","authenticated-orcid":true,"given":"Young-Kwon","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Surgery, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles (Y.-K.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2071-1243","authenticated-orcid":true,"given":"Martin A.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center, Department of Internal Medicine (H.P., S.L., J.F., M.A.S., L.H.Y., A.E.), Yale University School of Medicine, New Haven, CT."},{"name":"Departments of Cell Biology and Biomedical Engineering, Yale University, New Haven, CT. 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