{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T11:10:02Z","timestamp":1785150602702,"version":"3.55.0"},"reference-count":49,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T00:00:00Z","timestamp":1730246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense","doi-asserted-by":"publisher","award":["HT9425-24-1-0239"],"award-info":[{"award-number":["HT9425-24-1-0239"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense","doi-asserted-by":"publisher","award":["K08 HL 168240"],"award-info":[{"award-number":["K08 HL 168240"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense","doi-asserted-by":"publisher","award":["#R24HL123767"],"award-info":[{"award-number":["#R24HL123767"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH","award":["HT9425-24-1-0239"],"award-info":[{"award-number":["HT9425-24-1-0239"]}]},{"name":"NIH","award":["K08 HL 168240"],"award-info":[{"award-number":["K08 HL 168240"]}]},{"name":"NIH","award":["#R24HL123767"],"award-info":[{"award-number":["#R24HL123767"]}]},{"name":"NHLBI","award":["HT9425-24-1-0239"],"award-info":[{"award-number":["HT9425-24-1-0239"]}]},{"name":"NHLBI","award":["K08 HL 168240"],"award-info":[{"award-number":["K08 HL 168240"]}]},{"name":"NHLBI","award":["#R24HL123767"],"award-info":[{"award-number":["#R24HL123767"]}]},{"name":"Cardiovascular Medical Research and Education Fund (CMREF)","award":["HT9425-24-1-0239"],"award-info":[{"award-number":["HT9425-24-1-0239"]}]},{"name":"Cardiovascular Medical Research and Education Fund (CMREF)","award":["K08 HL 168240"],"award-info":[{"award-number":["K08 HL 168240"]}]},{"name":"Cardiovascular Medical Research and Education Fund (CMREF)","award":["#R24HL123767"],"award-info":[{"award-number":["#R24HL123767"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The role of stress granules (SGs) in pulmonary arterial hypertension (PAH) is unknown. We hypothesized that SG formation contributes to abnormal vascular phenotypes, and cardiac and skeletal muscle dysfunction in PAH. Using the rat Sugen\/hypoxia (SU\/Hx) model of PAH, we demonstrate the formation of SG puncta and increased expression of SG proteins compared to control animals in lungs, right ventricles, and soleus muscles. Acetazolamide (ACTZ) treatment ameliorated the disease and reduced SG formation in all of these tissues. Primary pulmonary artery smooth muscle cells (PASMCs) from diseased animals had increased SG protein expression and SG number after acute oxidative stress and this was ameliorated by ACTZ. Pharmacologic inhibition of SG formation or genetic ablation of the SG assembly protein (G3BP1) altered the SU\/Hx-PASMC phenotype by decreasing proliferation, increasing apoptosis and modulating synthetic and contractile marker expression. In human PAH lungs, we found increased SG puncta in pulmonary arteries compared to control lungs and in human PAH-PASMCs we found increased SGs after acute oxidative stress compared to healthy PASMCs. Genetic ablation of G3BP1 in human PAH-PASMCs resulted in a phenotypic switch to a less synthetic and more contractile phenotype. We conclude that increased SG formation in PASMCs and other tissues may contribute to PAH pathogenesis.<\/jats:p>","DOI":"10.3390\/cells13211796","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T09:10:44Z","timestamp":1730279444000},"page":"1796","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Stress Granule Assembly in Pulmonary Arterial Hypertension"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9712-2615","authenticated-orcid":false,"given":"Kosmas","family":"Kosmas","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Newborn Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimilia Eirini","family":"Papathanasiou","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Newborn Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fotios","family":"Spyropoulos","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Newborn Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1755-3416","authenticated-orcid":false,"given":"Rakhshinda","family":"Rehman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Newborn Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley Anne","family":"Cunha","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Newborn Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura E.","family":"Fredenburgh","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Greenburgh, NY 10591, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7219-7688","authenticated-orcid":false,"given":"Mark A.","family":"Perrella","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Newborn Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Medicine, Division of Pulmonary and Critical Care, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3104-4570","authenticated-orcid":false,"given":"Helen","family":"Christou","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Newborn Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1056\/NEJMra035488","article-title":"Pulmonary arterial hypertension","volume":"351","author":"Farber","year":"2004","journal-title":"N. 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