{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:47:05Z","timestamp":1791528425424,"version":"4.3.4"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2026,10,9]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Idiopathic pulmonary arterial hypertension (IPAH) is driven by progressive vascular remodeling, particularly smooth muscle cell (SMC) proliferation. Current combination vasodilator therapies have markedly improved outcomes; however, prognosis remains poor in subgroups such as patients with respiratory comorbidities. Elevation of intravascular hydrostatic pressure is a hallmark of IPAH, yet its direct role in pulmonary artery SMCs remains unclear. We aimed to identify pressure-responsive mediators using a newly developed hydrostatic pressurization system to model hypertensive hemodynamics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      Pulmonary artery SMCs from 4 patients with IPAH were exposed to high hydrostatic pressure (70\/40 mm\u2009Hg, 60 bpm). Transcriptomic profiling identified differentially expressed genes, which were validated by quantitative polymerase chain reaction. Functional studies included PIEZO1 (piezo type mechanosensitive ion channel component 1) modulation, rhSTC1 (recombinant human stanniocalcin-1) treatment, bromodeoxyuridine incorporation, and Western blotting for cell-cycle regulators. Chronic hypoxia\u2013induced pulmonary hypertension was assessed in wild-type and\n                      <jats:italic toggle=\"yes\">Stc1<\/jats:italic>\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                      mice by hemodynamic and histological analyses, with or without intratracheal rhSTC1 administration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      RNA sequencing revealed\n                      <jats:italic toggle=\"yes\">STC1<\/jats:italic>\n                      to be a pressure-induced gene in IPAH SMCs. PIEZO1 activation upregulated\n                      <jats:italic toggle=\"yes\">STC1<\/jats:italic>\n                      , whereas knockdown blunted this response.\n                      <jats:italic toggle=\"yes\">STC1<\/jats:italic>\n                      was upregulated in IPAH lungs, while rhSTC1 reduced pulmonary arterial SMC proliferation and increased p-p53, p21, and p27 expression.\n                      <jats:italic toggle=\"yes\">Stc1<\/jats:italic>\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                      mice under hypoxia exhibited significantly higher right ventricular systolic pressure and greater pulmonary arterial medial thickness than wild-type mice. CD68-positive macrophages were increased in\n                      <jats:italic toggle=\"yes\">Stc1<\/jats:italic>\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                      mice under normoxia and further elevated with hypoxia. Intratracheal administration of rhSTC1 attenuated PAH in wild-type and\n                      <jats:italic toggle=\"yes\">Stc1<\/jats:italic>\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                      mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>\n                      Elevated hydrostatic pressure drives\n                      <jats:italic toggle=\"yes\">STC1<\/jats:italic>\n                      expression via PIEZO1, suggesting an adaptive but insufficient protective response in IPAH. Modulation of STC1 (stanniocalcin-1) may represent a potential therapeutic approach.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.125.327869","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T09:00:14Z","timestamp":1788944414000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Mechanosensitive Stanniocalcin-1 Suppresses Smooth Muscle Cell Proliferation and Attenuates Experimental Pulmonary Hypertension"],"prefix":"10.1161","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2637-7872","authenticated-orcid":true,"given":"Mariko","family":"Kogami","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1535-1925","authenticated-orcid":true,"given":"Yuko","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical 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