{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T18:04:20Z","timestamp":1789581860937,"version":"build-2803163510"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by vasculopathy, inflammation, and fibrosis, in which pulmonary hypertension (PH) is a major cause of mortality. In SSc, the relationship between endothelial and platelet functions with echocardiographic findings have not been evaluated. Here, we evaluated the endothelial and platelet functions in SSc patients with different PH probability and tested their associations with echocardiographic parameters, including the maximal tricuspid regurgitant velocity (TRV\n                    <jats:sub>max<\/jats:sub>\n                    ). Endothelial function was assessed by flow-mediated dilation (FMD) of brachial artery and blood nitrite levels, measured by chemiluminescence method. Platelet activity was measured by light transmission aggregometry in response to stimulation by adenosine diphosphate (ADP) and thrombin receptor\u2013activating peptide-6 (TRAP-6). PH probability was assessed by echocardiography, and PH diagnosis was confirmed by right heart catheterization. SSc patients with PH probability had lower FMD than age-matched controls: FMD decreased from 13.3\u2009\u00b1\u20093.9% in controls to 5.6\u2009\u00b1\u20091.7%, 4.6\u2009\u00b1\u20090.4%, and 3.8\u2009\u00b1\u20090.4% in SSc patients with low PH probability, intermediate PH probability, and confirmed PH, respectively. SSc patients with PH had higher blood nitrite levels than controls or the patients with low PH probability. TRV\n                    <jats:sub>max<\/jats:sub>\n                    correlated inversely with FMD and positively with platelet aggregation. In multivariable regression analysis, TRAP-6-induced platelet aggregation and FMD were independently associated with TRV\n                    <jats:sub>max<\/jats:sub>\n                    . Furthermore, we demonstrated in two patients that nebulized sodium nitrite transiently reduced TRV\n                    <jats:sub>max<\/jats:sub>\n                    . In conclusion, SSc patients have endothelial dysfunction and increased platelet activity, which exhibits correlation with TRV\n                    <jats:sub>max<\/jats:sub>\n                    .\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0357987","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T17:42:54Z","timestamp":1789580574000},"page":"e0357987","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Endothelial and platelet dysfunction in systemic sclerosis with pulmonary hypertension"],"prefix":"10.1371","volume":"21","author":[{"given":"Thamonwan","family":"Imerbtham","sequence":"first","affiliation":[{"name":"Mahidol University","place":["Bangkok, Thailand"],"department":["Program in Translational Medicine, Faculty of Medicine Ramathibodi Hospital"]},{"name":"Naresuan University","place":["Phitsanulok, Thailand"],"department":["Department of Cardio-Thoracic Technology, Faculty of Allied Health Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanaporn","family":"Sriwantana","sequence":"additional","affiliation":[{"name":"Mahidol University","place":["Samut Prakan, Thailand"],"department":["Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pintip","family":"Ngamjanyaporn","sequence":"additional","affiliation":[{"name":"Mahidol University","place":["Bangkok, Thailand"],"department":["Division of Allergy Immunology and Rheumatology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanyaluck","family":"Sotananusak","sequence":"additional","affiliation":[{"name":"Mahidol University","place":["Samut Prakan, Thailand"],"department":["Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pipat","family":"Ngammisri","sequence":"additional","affiliation":[{"name":"Mahidol University","place":["Samut Prakan, Thailand"],"department":["Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krittimeth","family":"Trerayapiwat","sequence":"additional","affiliation":[{"name":"Mahidol University","place":["Samut Prakan, Thailand"],"department":["Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panu","family":"Dumrongkitchaiporn","sequence":"additional","affiliation":[{"name":"Mahidol University","place":["Samut Prakan, Thailand"],"department":["Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi 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Ludwicka","year":"1995","journal-title":"J Rheumatol"},{"issue":"4","key":"pone.0357987.ref030","doi-asserted-by":"crossref","first-page":"103290","DOI":"10.1016\/j.autrev.2023.103290","article-title":"The role of TAPSE\/sPAP ratio in predicting pulmonary hypertension and mortality in the systemic sclerosis EUSTAR cohort","volume":"22","author":"A Colalillo","year":"2023","journal-title":"Autoimmun Rev"},{"issue":"7","key":"pone.0357987.ref031","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1161\/CIRCRESAHA.116.309184","article-title":"Inhaled sodium nitrite improves rest and exercise hemodynamics in heart failure with preserved ejection fraction","volume":"119","author":"BA Borlaug","year":"2016","journal-title":"Circ Res"},{"issue":"10","key":"pone.0357987.ref032","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1038\/nm1109","article-title":"Inhaled nebulized nitrite is a hypoxia-sensitive NO-dependent selective pulmonary vasodilator","volume":"10","author":"CJ 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