Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Nov;17(11):e012067.
doi: 10.1161/CIRCHEARTFAILURE.124.012067. Epub 2024 Oct 22.

Proteomic Signatures of Right Ventricular Outcomes in Pulmonary Arterial Hypertension

Hongyang Pi  1 , Lu Xia  2 , Olivier Boucherat  3 , Karthik Suresh  4 , Anna R Hemnes  5 , Sébastien Bonnet  3 , Claudio A Bravo  6 , Laura Oppegard  7 , Samuel G Rayner  1 , Ali Shojaie  8 , Sina A Gharib #  1 , Peter J Leary #  1   9
Affiliations

Proteomic Signatures of Right Ventricular Outcomes in Pulmonary Arterial Hypertension

Hongyang Pi et al. Circ Heart Fail. 2024 Nov.

Abstract

Background: Pulmonary arterial hypertension (PAH) is a disease of progressive right ventricular (RV) failure with high morbidity and mortality. Our goal is to investigate proteomic features and pathways associated with RV-focused outcomes including mortality, RV dilation, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) in PAH.

Methods: Participants in a single-institution cohort with 3 years of follow-up underwent proteomic profiling of their plasma using 7288 aptamers (targeting 6467 unique human proteins). Partial least squares discriminant analysis was performed to assess global protein variation associated with mortality, RV dilation, and NT-proBNP levels. Differentially abundant proteins and enriched pathways associated with outcomes were identified following baseline adjustments. RV vulnerability models estimated associations for individuals with similar afterload following adjustment for pulmonary vascular resistance.

Results: A total of 117 participants with PAH were included. Partial least squares discriminant analysis of the proteome showed clear separation between survivors and nonsurvivors, participants with dilated versus nondilated RVs, and across NT-proBNP levels. Proteins and pathways involving the ECM (extracellular matrix) were upregulated in participants who died during follow-up, those with severe RV dilation, and those with higher levels of NT-proBNP. Pulmonary vascular resistance adjustment reinforced the importance of ECM proteins in the association with RV vulnerability, independent of afterload. These findings were confirmed in independent PAH cohorts with available plasma proteomics and RV tissue gene and protein expression.

Conclusions: Distinct plasma proteomic profiles are associated with mortality, RV dilation, and NT-proBNP in PAH. Proteins and pathways governing tissue remodeling are strongly associated with poor outcomes, may mediate RV vulnerability to right heart failure, and represent promising candidates as biomarkers and potential therapeutic targets.

Keywords: biomarkers; extracellular matrix; proteomics; pulmonary arterial hypertension; right ventricle; right-sided heart failure; survivors.

PubMed Disclaimer

Conflict of interest statement

Drs Pi, Suresh, Hemnes, Bravo, Rayner, Shojaie, Leary, and Gharib have received research funding from the National Institutes of Health. Dr Hemnes has done consulting work for GossamerBio, United Therapeutics, Janssen, Merck, and Tenax Therapeutics. She is a stockholder (negligible value) in Tenax Therapeutics. Dr Rayner received research funding from Bayer Pharmaceuticals and United Therapeutics. Dr Leary has received grants and research support from the CHEST Foundation, the American Heart Association, Bayer, Janssen, and Acceleron/Merck. He has been a grant review consultant for Bayer and has adjudicated clinical end points for Sumitomo Pharma. He is on the scientific leadership council for the Pulmonary Hypertension Association and the medical advisory board for Team PHenomenal Hope. The other authors report no conflicts.

References

    1. Tuder RM, Archer SL, Dorfmüller P, Erzurum SC, Guignabert C, Michelakis E, Rabinovitch M, Schermuly R, Stenmark KR, Morrell NW. Relevant issues in the pathology and pathobiology of pulmonary hypertension. J Am Coll Cardiol 2013;62:D4–12. - PMC - PubMed
    1. Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M, Carlsen J, Coats AJS, Escribano-Subias P, Ferrari P, et al. the ESC/ERS Scientific Document Group. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J 2022;43:3618–3731.
    1. D’Alonzo GE, Barts RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, Fisherman AP, Goldring RM, Groves BM, Kernis JT, et al. Survival in Patients with Primary Pulmonary Hypertension. Ann Intern Med 1991;115:343–349. - PubMed
    1. Campo A, Mathai SC, Le Pavec J, Zaiman AL, Hummers LK, Boyce D, Housten T, Lechtzin N, Chami H, Girgis RE, et al. Outcomes of hospitalisation for right heart failure in pulmonary arterial hypertension. Eur Respir J 2011;38:359–367. - PubMed
    1. Schwenk JM, Omenn GS, Sun Z, Campbell DS, Baker MS, Overall CM, Aebersold R, Moritz RL, Deutsch EW. The human plasma proteome draft of 2017: building on the human plasma peptideatlas from mass spectrometry and complementary assays. J Proteome Res 2017;16:4299–4310. - PMC - PubMed

LinkOut - more resources