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Prognostic Significance of Proteomics-Discovered Circulating Inflammatory Biomarkers in Patients With Pulmonary Arterial Hypertension.
Yokokawa, Tetsuro; Boucherat, Olivier; Martineau, Sandra; Lemay, Sarah-Eve; Breuils-Bonnet, Sandra; Krishna, Vinod; Kalyana-Sundaram, Shanker; Jeyaseelan, Jey; Potus, François; Bonnet, Sébastien; Provencher, Steeve.
Afiliação
  • Yokokawa T; Pulmonary Hypertension Research Group Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec Québec City Québec Canada.
  • Boucherat O; Department of Cardiovascular Medicine Fukushima Medical University Fukushima Japan.
  • Martineau S; Pulmonary Hypertension Research Group Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec Québec City Québec Canada.
  • Lemay SE; Department of Medicine Université Laval Québec City Québec Canada.
  • Breuils-Bonnet S; Pulmonary Hypertension Research Group Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec Québec City Québec Canada.
  • Krishna V; Pulmonary Hypertension Research Group Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec Québec City Québec Canada.
  • Kalyana-Sundaram S; Pulmonary Hypertension Research Group Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec Québec City Québec Canada.
  • Jeyaseelan J; Janssen Research & Development Spring House PA USA.
  • Potus F; Janssen Research & Development Spring House PA USA.
  • Bonnet S; Janssen Research & Development Spring House PA USA.
  • Provencher S; Pulmonary Hypertension Research Group Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec Québec City Québec Canada.
J Am Heart Assoc ; 13(12): e032888, 2024 Jun 18.
Article em En | MEDLINE | ID: mdl-38874078
ABSTRACT

BACKGROUND:

Pulmonary arterial hypertension (PAH) ultimately leads to right ventricular failure and premature death. The identification of circulating biomarkers with prognostic utility is considered a priority. As chronic inflammation is recognized as key pathogenic driver, we sought to identify inflammation-related circulating proteins that add incremental value to current risk stratification models for long-term survival in patients with PAH. METHODS AND

RESULTS:

Plasma levels of 384 inflammatory proteins were measured with the proximity extension assay technology in patients with PAH (n=60) and controls with normal hemodynamics (n=28). Among these, 51 analytes were significantly overexpressed in the plasma of patients with PAH compared with controls. Cox proportional hazard analyses and C-statistics were performed to assess the prognostic value and the incremental prognostic value of differentially expressed proteins. A panel of 6 proteins (CRIM1 [cysteine rich transmembrane bone morphogenetic protein regulator 1], HGF [hepatocyte growth factor], FSTL3 [follistatin-like 3], PLAUR [plasminogen activator, urokinase receptor], CLSTN2 [calsyntenin 2], SPON1 [spondin 1]) were independently associated with death/lung transplantation at the time of PAH diagnosis after adjustment for the 2015 European Society of Cardiology/European Respiratory Society guidelines, the REVEAL (Registry to Evaluate Early and Long-Term PAH Disease Management) 2.0 risk scores, and the refined 4-strata risk assessment. CRIM1, PLAUR, FSTL3, and SPON1 showed incremental prognostic value on top of the predictive models. As determined by Western blot, FSTL3 and SPON1 were significantly upregulated in the right ventricle of patients with PAH and animal models (monocrotaline-injected and pulmonary artery banding-subjected rats).

CONCLUSIONS:

In addition to revealing new actors likely involved in cardiopulmonary remodeling in PAH, our screening identified promising circulating biomarkers to improve risk prediction in PAH, which should be externally confirmed.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Biomarcadores / Proteômica / Hipertensão Arterial Pulmonar Limite: Adult / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: J Am Heart Assoc Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Biomarcadores / Proteômica / Hipertensão Arterial Pulmonar Limite: Adult / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: J Am Heart Assoc Ano de publicação: 2024 Tipo de documento: Article