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Peer-reviewedCC BY 4.0PLOS One

Endothelial and platelet dysfunction in systemic sclerosis with pulmonary hypertension

  • Thamonwan Imerbtham1
  • Thanaporn Sriwantana2
  • Pintip Ngamjanyaporn3
  • Thanyaluck Sotananusak4
  • Pipat Ngammisri5
  • Krittimeth Trerayapiwat
  • Panu Dumrongkitchaiporn
  • Prapaporn Pisitkun
  • Sirada Srihirun
  • Pornpun Vivithanaporn
  • Nathawut Sibmooh
5 affiliations
  1. 1Program in Translational Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
  2. 2Department of Cardio-Thoracic Technology, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok, Thailand
  3. 3Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, Thailand
  4. 4Division of Allergy Immunology and Rheumatology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
  5. 5Department of Pharmacology, Faculty of Dentistry, Mahidol University, Bangkok, Thailand
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Abstract

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 (TRVmax). 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–activating 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 ± 3.9% in controls to 5.6 ± 1.7%, 4.6 ± 0.4%, and 3.8 ± 0.4% 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. TRVmax correlated inversely with FMD and positively with platelet aggregation. In multivariable regression analysis, TRAP-6-induced platelet aggregation and FMD were independently associated with TRVmax. Furthermore, we demonstrated in two patients that nebulized sodium nitrite transiently reduced TRVmax. In conclusion, SSc patients have endothelial dysfunction and increased platelet activity, which exhibits correlation with TRVmax.

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Cite

BibTeXRIS
BibTeX
@article{imerbtham2026endothelial,
  title = {{Endothelial and platelet dysfunction in systemic sclerosis with pulmonary hypertension}},
  author = {Thamonwan Imerbtham and Thanaporn Sriwantana and Pintip Ngamjanyaporn and Thanyaluck Sotananusak and Pipat Ngammisri and Krittimeth Trerayapiwat and Panu Dumrongkitchaiporn and Prapaporn Pisitkun and Sirada Srihirun and Pornpun Vivithanaporn and Nathawut Sibmooh},
  journal = {PLOS One},
  year = {2026},
  month = sep,
  doi = {10.1371/journal.pone.0357987},
  url = {https://doi.org/10.1371/journal.pone.0357987},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Endothelial and platelet dysfunction in systemic sclerosis with pulmonary hypertension
AU  - Thamonwan Imerbtham
AU  - Thanaporn Sriwantana
AU  - Pintip Ngamjanyaporn
AU  - Thanyaluck Sotananusak
AU  - Pipat Ngammisri
AU  - Krittimeth Trerayapiwat
AU  - Panu Dumrongkitchaiporn
AU  - Prapaporn Pisitkun
AU  - Sirada Srihirun
AU  - Pornpun Vivithanaporn
AU  - Nathawut Sibmooh
PY  - 2026
DA  - 2026/09/16
JO  - PLOS One
DO  - 10.1371/journal.pone.0357987
UR  - https://doi.org/10.1371/journal.pone.0357987
AB  - 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 (TRVmax). 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–activating 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 ± 3.9% in controls to 5.6 ± 1.7%, 4.6 ± 0.4%, and 3.8 ± 0.4% 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. TRVmax correlated inversely with FMD and positively with platelet aggregation. In multivariable regression analysis, TRAP-6-induced platelet aggregation and FMD were independently associated with TRVmax. Furthermore, we demonstrated in two patients that nebulized sodium nitrite transiently reduced TRVmax. In conclusion, SSc patients have endothelial dysfunction and increased platelet activity, which exhibits correlation with TRVmax.
SN  - 1932-6203
ER  -