Transpulmonary Proteome Gradients Identify Pathways Involved in Pulmonary Vascular Disease Due To Heart Failure
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F25%3A00086087" target="_blank" >RIV/00023001:_____/25:00086087 - isvavai.cz</a>
Result on the web
<a href="https://www.ahajournals.org/doi/epdf/10.1161/CIRCHEARTFAILURE.125.013208" target="_blank" >https://www.ahajournals.org/doi/epdf/10.1161/CIRCHEARTFAILURE.125.013208</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1161/CIRCHEARTFAILURE.125.013208" target="_blank" >10.1161/CIRCHEARTFAILURE.125.013208</a>
Alternative languages
Result language
angličtina
Original language name
Transpulmonary Proteome Gradients Identify Pathways Involved in Pulmonary Vascular Disease Due To Heart Failure
Original language description
BACKGROUND:Some, but not all, patients with heart failure (HF) develop pulmonary vascular disease (PVD), which contributes to poor prognosis. Mechanisms leading to PVD in HF are poorly understood. We aimed to analyze transpulmonary gradients of proteins consumed or elaborated across the lungs to identify mediators of PVD by unbiased proteomics.METHODS:Overall, 21 controls and 160 patients with HF with reduced ejection fraction underwent pulmonary artery catheterization with blood sampling from postcapillary (wedged balloon) and precapillary (unwedged) position to obtain transpulmonary gradients. The samples from controls and HF from the highest (Q4, n=40) and lowest quartile (Q1, n=40) of pulmonary vascular resistance (PVR) were analyzed using the proteomic proximity extension assay (Olink) of 275 proteins. Venous blood concentrations or transpulmonary gradients were analyzed to identify biomarkers or potential mediators of PVD.RESULTS:Comparison of Q1 and Q4 of PVR identified PSP-D (pulmonary surfactant-associated protein D) as a marker of PVD. Examination of gradients across the lungs in high PVR HF revealed significant uptake of 18 proteins, mostly associated with inflammation (chemokines, oncostatin-M, MMP9 [matrix metalloproteinase 9]) or with TGF (transforming growth factor)/activin pathway (GDF2 [growth differentiation factor 2]/BMP9 [bone morphogenic protein 9]), and release of 5 proteins, notably IL (interleukin) 6 and IL33. In contrast, these protein gradients were negligible in controls and low PVR patients with HF. Active pulmonary release of IL6 contributed to systemic elevation of IL6 and correlated with right ventricular function.CONCLUSIONS:The lungs of patients with HF with high PVR display abnormal uptake and release of proinflammatory cytokines from IL6/gp130 family (IL6, IL33, oncostatin-M), along with increased transpulmonary uptake of GDF2/BMP9. The study shows that proteins orchestrating inflammation or pulmonary vessel remodeling in group 1 pulmonary hypertension, are also operating in patients with PVD due to HF.REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT06331208.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30201 - Cardiac and Cardiovascular systems
Result continuities
Project
<a href="/en/project/NU22-02-00161" target="_blank" >NU22-02-00161: Mechanisms of pulmonary vascular dysfunction in heart failure (LUNG-HF)</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Circulation. Heart failure
ISSN
1941-3289
e-ISSN
1941-3297
Volume of the periodical
18
Issue of the periodical within the volume
12
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
"art. no. e013208"
UT code for WoS article
001639376300001
EID of the result in the Scopus database
2-s2.0-105023656304