{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:14:56Z","timestamp":1790615696751,"version":"4.1.0"},"reference-count":65,"publisher":"American Society for Clinical Investigation","issue":"9","license":[{"start":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T00:00:00Z","timestamp":1652054400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"crossref","award":["HL098967,DK107870,HL140411"],"award-info":[{"award-number":["HL098967,DK107870,HL140411"]}],"id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001747","name":"Armstrong McDonald Foundation","doi-asserted-by":"crossref","award":["grant"],"award-info":[{"award-number":["grant"]}],"id":[{"id":"10.13039\/100001747","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,9]]},"abstract":"<jats:p>\n                    Patients with hereditary hemorrhagic telangiectasia (HHT) have arteriovenous malformations (AVMs) with genetic mutations involving the activin-A receptor like type 1 (\n                    <jats:italic>ACVRL1<\/jats:italic>\n                    or\n                    <jats:italic>ALK1<\/jats:italic>\n                    ) and endoglin (\n                    <jats:italic>ENG<\/jats:italic>\n                    ). Recent studies have shown that Neuropilin-1 (NRP-1) inhibits ALK1. We investigated the expression of NRP-1 in livers of patients with HHT and found that there was a significant reduction in NRP-1 in perivascular smooth muscle cells (SMCs). We used\n                    <jats:italic>\n                      Nrp1\n                      <jats:sup>SM22KO<\/jats:sup>\n                    <\/jats:italic>\n                    mice (\n                    <jats:italic>Nrp1<\/jats:italic>\n                    was ablated in SMCs) and found hemorrhage, increased immune cell infiltration with a decrease in SMCs, and pericyte lining in lungs and liver in adult mice. Histologic examination revealed lung arteriovenous fistulas (AVFs) with enlarged liver vessels. Evaluation of the retina vessels at P5 from\n                    <jats:italic>\n                      Nrp1\n                      <jats:sup>SM22KO<\/jats:sup>\n                    <\/jats:italic>\n                    mice demonstrated dilated capillaries with a reduction of pericytes. In inflow artery of surgical AVFs from the\n                    <jats:italic>\n                      Nrp1\n                      <jats:sup>SM22KO<\/jats:sup>\n                    <\/jats:italic>\n                    versus WT mice\n                    <jats:italic>,<\/jats:italic>\n                    there was a significant decrease in\n                    <jats:italic>Tgfb1<\/jats:italic>\n                    ,\n                    <jats:italic>Eng<\/jats:italic>\n                    , and\n                    <jats:italic>Alk1<\/jats:italic>\n                    expression and phosphorylated SMAD1\/5\/8 (pSMAD1\/5\/8), with an increase in apoptosis. TGF-\u03b21\u2013stimulated aortic SMCs from\n                    <jats:italic>\n                      Nrp1\n                      <jats:sup>SM22KO<\/jats:sup>\n                    <\/jats:italic>\n                    versus WT mice have decreased pSMAD1\/5\/8 and increased apoptosis. Coimmunoprecipitation experiments revealed that NRP-1 interacts with ALK1 and ENG in SMCs. In summary, NRP-1 deletion in SMCs leads to reduced ALK1, ENG, and pSMAD1\/5\/8 signaling and reduced cell death associated with AVM formation.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.155565","type":"journal-article","created":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T12:00:32Z","timestamp":1649160032000},"source":"Crossref","is-referenced-by-count":9,"title":["Neuropilin-1 deficiency in vascular smooth muscle cells is associated with hereditary hemorrhagic telangiectasia arteriovenous malformations"],"prefix":"10.1172","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9149-7360","authenticated-orcid":true,"given":"Sreenivasulu","family":"Kilari","sequence":"first","affiliation":[{"name":"Vascular and Interventional Radiology Translational laboratory, Division of Vascular and Interventional Radiology, Department of 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