PMID- 33334941
OWN - NLM
STAT- MEDLINE
DCOM- 20210702
LR  - 20231109
IS  - 1399-3003 (Electronic)
IS  - 0903-1936 (Print)
IS  - 0903-1936 (Linking)
VI  - 57
IP  - 4
DP  - 2021 Apr
TI  - Targeted proteomics of right heart adaptation to pulmonary arterial hypertension.
LID - 10.1183/13993003.02428-2020 [doi]
LID - 2002428
AB  - No prior proteomic screening study has centred 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 
      (discovery cohort) and 76 (validation cohort) PAH patients. The association 
      between proteomic markers and RHMP, defined by the Mayo right heart score 
      (combining RV strain, New York Heart Association (NYHA) class and N-terminal 
      pro-brain natriuretic peptide (NT-proBNP)) and Stanford score (RV end-systolic 
      remodelling index, NYHA class and NT-proBNP), was assessed by partial least 
      squares regression. Biomarker expression was measured in RV samples from PAH 
      patients and controls, and pulmonary artery banding (PAB) mice.High levels of 
      hepatocyte 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 of heart failure who warrant closer follow-up and 
      intensified therapy.
CI  - Copyright (c)ERS 2021.
FAU - Amsallem, Myriam
AU  - Amsallem M
AD  - Division of Cardiovascular Medicine, Stanford University School of Medicine, 
      Stanford, CA, USA.
AD  - Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, 
      USA.
AD  - Vera Moulton Wall Center at Stanford, Stanford University School of Medicine, 
      Stanford, CA, USA.
AD  - Both first authors contributed equally.
FAU - Sweatt, Andrew J
AU  - Sweatt AJ
AD  - Vera Moulton Wall Center at Stanford, Stanford University School of Medicine, 
      Stanford, CA, USA.
AD  - Division of Pulmonary and Critical Care Medicine, Stanford University School of 
      Medicine, Stanford, CA, USA.
AD  - Both first authors contributed equally.
FAU - Arthur Ataam, Jennifer
AU  - Arthur Ataam J
AD  - Division of Cardiovascular Medicine, Stanford University School of Medicine, 
      Stanford, CA, USA.
AD  - Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, 
      USA.
FAU - Guihaire, Julien
AU  - Guihaire J
AD  - Research and Innovation Laboratory, INSERM U999, Marie Lannelongue Hospital, 
      Paris Sud Saclay University, Le Plessis Robinson, France.
FAU - Lecerf, Florence
AU  - Lecerf F
AD  - Research and Innovation Laboratory, INSERM U999, Marie Lannelongue Hospital, 
      Paris Sud Saclay University, Le Plessis Robinson, France.
FAU - Lambert, Melanie
AU  - Lambert M
AD  - Research and Innovation Laboratory, INSERM U999, Marie Lannelongue Hospital, 
      Paris Sud Saclay University, Le Plessis Robinson, France.
FAU - Ghigna, Maria Rosa
AU  - Ghigna MR
AUID- ORCID: 0000-0001-5996-665X
AD  - Division of Pathology, Marie Lannelongue Hospital, Le Plessis Robinson, France.
FAU - Ali, Md Khadem
AU  - Ali MK
AD  - Vera Moulton Wall Center at Stanford, Stanford University School of Medicine, 
      Stanford, CA, USA.
AD  - Division of Pulmonary and Critical Care Medicine, Stanford University School of 
      Medicine, Stanford, CA, USA.
FAU - Mao, Yuqiang
AU  - Mao Y
AD  - Vera Moulton Wall Center at Stanford, Stanford University School of Medicine, 
      Stanford, CA, USA.
AD  - Division of Pulmonary and Critical Care Medicine, Stanford University School of 
      Medicine, Stanford, CA, USA.
FAU - Fadel, Elie
AU  - Fadel E
AD  - Division of Pathology, Marie Lannelongue Hospital, Le Plessis Robinson, France.
FAU - Rabinovitch, Marlene
AU  - Rabinovitch M
AD  - Vera Moulton Wall Center at Stanford, Stanford University School of Medicine, 
      Stanford, CA, USA.
AD  - Division of Pediatrics, Stanford University School of Medicine, Stanford, CA, 
      USA.
FAU - de Jesus Perez, Vinicio
AU  - de Jesus Perez V
AD  - Vera Moulton Wall Center at Stanford, Stanford University School of Medicine, 
      Stanford, CA, USA.
AD  - Division of Pulmonary and Critical Care Medicine, Stanford University School of 
      Medicine, Stanford, CA, USA.
FAU - Spiekerkoetter, Edda
AU  - Spiekerkoetter E
AD  - Vera Moulton Wall Center at Stanford, Stanford University School of Medicine, 
      Stanford, CA, USA.
AD  - Division of Pulmonary and Critical Care Medicine, Stanford University School of 
      Medicine, Stanford, CA, USA.
FAU - Mercier, Olaf
AU  - Mercier O
AD  - Research and Innovation Laboratory, INSERM U999, Marie Lannelongue Hospital, 
      Paris Sud Saclay University, Le Plessis Robinson, France.
FAU - Haddad, Francois
AU  - Haddad F
AD  - Division of Cardiovascular Medicine, Stanford University School of Medicine, 
      Stanford, CA, USA.
AD  - Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, 
      USA.
AD  - Vera Moulton Wall Center at Stanford, Stanford University School of Medicine, 
      Stanford, CA, USA.
AD  - Both senior authors contributed equally.
FAU - Zamanian, Roham T
AU  - Zamanian RT
AD  - Vera Moulton Wall Center at Stanford, Stanford University School of Medicine, 
      Stanford, CA, USA.
AD  - Division of Pulmonary and Critical Care Medicine, Stanford University School of 
      Medicine, Stanford, CA, USA.
AD  - Both senior authors contributed equally.
LA  - eng
GR  - K23 HL151892/HL/NHLBI NIH HHS/United States
GR  - P01 HL108797/HL/NHLBI NIH HHS/United States
GR  - R01 HL128734/HL/NHLBI NIH HHS/United States
GR  - R01 HL158868/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210408
PL  - England
TA  - Eur Respir J
JT  - The European respiratory journal
JID - 8803460
RN  - 114471-18-0 (Natriuretic Peptide, Brain)
SB  - IM
CIN - Eur Respir J. 2021 Apr 8;57(4):. PMID: 33833075
MH  - Animals
MH  - Cohort Studies
MH  - Familial Primary Pulmonary Hypertension
MH  - Humans
MH  - *Hypertension, Pulmonary
MH  - Mice
MH  - Natriuretic Peptide, Brain
MH  - Proteomics
MH  - *Pulmonary Arterial Hypertension
PMC - PMC8029214
COIS- Conflict of interest: M. Amsallem has received a 2016 Young Investigator Seed 
      Grant from the Vera Moulton Wall Center at Stanford, a 2019-2020 Stanford 
      Maternal and Child Health Research Institute research seed grant, a research 
      grant from Actelion-Janssen and speaker fees from Bayer. Conflict of interest: 
      A.J. Sweatt has nothing to disclose. Conflict of interest: J. Arthur Ataam has 
      nothing to disclose. Conflict of interest: J. Guihaire has nothing to disclose. 
      Conflict of interest: F. Lecerf has nothing to disclose. Conflict of interest: M. 
      Lambert has nothing to disclose. Conflict of interest: M.R. Ghigna has nothing to 
      disclose. Conflict of interest: M.K. Ali has nothing to disclose. Conflict of 
      interest: Y. Mao has nothing to disclose. Conflict of interest: E. Fadel has 
      nothing to disclose. Conflict of interest: M. Rabinovitch has nothing to 
      disclose. Conflict of interest: V. de Jesus Perez has nothing to disclose. 
      Conflict of interest: E. Spiekerkoetter is funded by Stanford Cardiovascular 
      Institute, National Heart Lung Blood Institute (NHLBI) at the National Institute 
      of Health (NIH) grant R01 HL128734 and Department of Defense grant PR161256. 
      Conflict of interest: O. Mercier has been supported by a public grant overseen by 
      the French National Research Agency as part of the second Investissement d'Avenir 
      program (ANR-15-RHUS-0002). Conflict of interest: F. Haddad has received research 
      grants from Actelion-Janssen and Philips. Conflict of interest: R.T. Zamanian has 
      nothing to disclose.
EDAT- 2020/12/19 06:00
MHDA- 2021/07/03 06:00
PMCR- 2021/04/08
CRDT- 2020/12/18 05:40
PHST- 2020/06/20 00:00 [received]
PHST- 2020/10/06 00:00 [accepted]
PHST- 2020/12/19 06:00 [pubmed]
PHST- 2021/07/03 06:00 [medline]
PHST- 2020/12/18 05:40 [entrez]
PHST- 2021/04/08 00:00 [pmc-release]
AID - 13993003.02428-2020 [pii]
AID - ERJ-02428-2020 [pii]
AID - 10.1183/13993003.02428-2020 [doi]
PST - epublish
SO  - Eur Respir J. 2021 Apr 8;57(4):2002428. doi: 10.1183/13993003.02428-2020. Print 
      2021 Apr.