Abstract
No prior proteomic screening study has centered on the right ventricle (RV) in pulmonary arterial hypertension (PAH). This study investigates the circulating proteomic profile associated with right heart maladaptive phenotype (RHMP) in PAH.
Plasma proteomic profiling was performed using multiplex immunoassay in 121 PAH patients (discovery cohort) and 76 patients (validation cohort). The association between proteomic markers and RHMP (defined by the Mayo right heart score [combining RV strain, New York Heart Association NYHA class and NT-proBNP] and Stanford score [RV end-systolic remodelling index, NYHA and NT-proBNP]) was assessed by partial least squares regression. Biomarkers expressions were measured in RV samples from PAH patients and controls, and pulmonary artery banding (PAB) mice.
High levels of hepatic growth factor (HGF), stem cell growth factor beta, nerve growth factor and stromal derived factor-1 were associated with worse Mayo and Stanford scores independently from pulmonary resistance or pressure in both cohorts (the validation cohort had more severe disease features: lower cardiac index and higher NT-proBNP). In both cohorts, HGF added value to the REVEAL score in the prediction of death, transplant, or hospitalisation at 3 years. RV expression levels of HGF and its receptor c-Met were higher in end-stage PAH patients than controls, and in PAB mice than shams.
High plasma HGF levels are associated with RHMP and predictive of 3-year clinical worsening. Both HGF and c-Met RV expression levels are increased in PAH. Assessing plasma HGF levels might identify patients at risk for heart failure who warrant closer follow-up and intensified therapy.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Dr. Yan reports grants from National Institutes of Health, during the conduct of the study;.
Conflict of interest: Dr. Amsallem has nothing to disclose.
Conflict of interest: Dr. Sweatt has nothing to disclose.
Conflict of interest: Dr. ARTHUR ATAAM has nothing to disclose.
Conflict of interest: Dr. Guihaire MD PhD has nothing to disclose.
Conflict of interest: Dr. LECERF has nothing to disclose.
Conflict of interest: Dr. LAMBERT PHD has nothing to disclose.
Conflict of interest: Dr. Ghigna has nothing to disclose.
Conflict of interest: Dr. Ali has nothing to disclose.
Conflict of interest: Dr. Mao has nothing to disclose.
Conflict of interest: Dr. FADEL has nothing to disclose.
Conflict of interest: Dr. RABINOVITCH has nothing to disclose.
Conflict of interest: Dr. de Jesus Perez has nothing to disclose.
Conflict of interest: Dr. Spiekerkoetter has nothing to disclose.
Conflict of interest: Dr. MERCIER has nothing to disclose.
Conflict of interest: Dr. HADDAD has nothing to disclose.
Conflict of interest: Dr. Zamanian has nothing to disclose.
- Received June 20, 2020.
- Accepted October 6, 2020.
- Copyright ©ERS 2020