Evidence map›Paper›PMID 41446146›Full record

ArticlebioRxiv : the preprint server for biology2025

Multicenter HFpEF study identifies sex disparity linked with two discrete cardiac proteomic signatures.

Aleksandra Binek, Johannes V Janssens, Niveda Sundararaman, Yaqun Teng, Kim M Mellor, Antonia J A Raaijmakers, Claire L Curl, Lizhuo Ai, Lawrence S C Czer, Amy D Bradshaw and 8 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Aleksandra BinekSmidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID 0000-0001-5764-7137
Johannes V JanssensSmidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID 0000-0002-7494-7702
Niveda SundararamanSmidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Yaqun TengSmidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Kim M MellorDepartment of Physiology, University of Auckland, Auckland, New Zealand.
Antonia J A RaaijmakersDepartment of Anatomy and Physiology, University of Melbourne, Melbourne, Victoria, Australia.
Claire L CurlDepartment of Anatomy and Physiology, University of Melbourne, Melbourne, Victoria, Australia.
Lizhuo AiSmidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Lawrence S C CzerSmidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Amy D BradshawDepartment of Medicine, Medical University of South Carolina, Charleston, SC, USA.
Kavita SharmaDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Virginia S HahnDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Kenneth S CampbellDivision of Cardiovascular Medicine, University of Kentucky, Lexington, KY, USA.ORCID 0000-0001-5615-5958
Michael R ZileDepartment of Medicine, Medical University of South Carolina, Charleston, SC, USA.
David A KassDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.ORCID 0000-0003-1596-2299
Eduardo MarbanSmidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Lea M D DelbridgeDepartment of Anatomy and Physiology, University of Melbourne, Melbourne, Victoria, Australia.
Jennifer E Van EykSmidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Funding

Intersection of Obesity and Heart Failure with Preserved Ejection FractionR35HL166565 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI David Alan Kass · 2023 to 2026
$4.1M
Exosome Therapeutics to Dissect HFpEF MechanismsR01HL155346 · NHLBI · CEDARS-SINAI MEDICAL CENTER · PI MARBAN, EDUARDO, VAN EYK, JENNIFER E · 2021 to 2024
$3.3M
Regulation of the Dynamic Proteome after Ischemic InjuryR01HL144509 · NHLBI · CEDARS-SINAI MEDICAL CENTER · PI GOTTLIEB, ROBERTA A., VAN EYK, JENNIFER E · 2019 to 2022
$2.9M
Length-dependent activation in human myocardiumR01HL149164 · NHLBI · UNIVERSITY OF KENTUCKY · PI CAMPBELL, KENNETH S, TANNER, BERTRAND C.W. · 2020 to 2023
$2.8M
Data-driven optimization of therapy for heart failureR01HL163977 · NHLBI · UNIVERSITY OF KENTUCKY · PI CAMPBELL, KENNETH S, LEE, LIK CHUAN · 2022 to 2025
$2.4M
Analysis of Single Cell Transcriptomics and Cardiac Metabolism in Heart Failure with Preserved Ejection FractionK23HL166770 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI Virginia Shalkey Hahn · 2023 to 2026
$792k
BLRD VA I01 BX005943NHLBI NIH HHS K23 HL166770NHLBI NIH HHS R01 HL144509NHLBI NIH HHS R01 HL149164NHLBI NIH HHS R01 HL155346NHLBI NIH HHS R01 HL163977NHLBI NIH HHS R35 HL166565
6 · The paper itself

Abstract

Heart failure with preserved ejection fraction (HFpEF) is epidemic, with an incidence exceeding that of heart failure with reduced ejection fraction (HFrEF). Sex differences in HFpEF phenotype have been observed, particularly linked to aging and metabolic comorbidities in women. Here, we report a multi-centre proteomic analysis of HFpEF and HFrEF cardiac samples. Using tissues and clinical data derived from multiple institutional biobanks, in-depth characterization of the proteome of ventricular samples was undertaken. Relative to HFrEF, the HFpEF cohort exhibited minimal proteome composition overlap and pronounced heterogeneity. A key finding of this investigation is that sex per se did not confer a distinctive proteomic HFpEF signature. Rather, two HFpEF proteomic profiles were identified, differing significantly in sex ratios. The identification of two Clusters revealed that HFpEF has two predominant proteomic signatures at the molecular level, marked by differences in the extent and nature of structural and contractile machinery and by local cellular and ECM communications. Upstream regulator analysis identified various molecular leads to be pursued in defining these two HFpEF profiles. Our findings offer specific opportunities for new exploration of therapeutic options to target the spectrum of HFpEF proteomic diversity and identify potential drug targeting prospects.

Indexed as

cardiac proteomicscardiomyocyte mechanismsHFpEFHFrEFmulti-center studysex

Identifiers

PMID41446146
PMCPMC12724455

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.