Identifying plasma proteomic signatures from health to heart failure, across the ejection fraction spectrum

Karolina Andrzejczyk; Sabrina Abou Kamar; Anne-Mar van Ommen; Elisa Dal Canto; Teun B Petersen; Gideon Valstar; K Martijn Akkerhuis; Maarten Jan Cramer; Victor Umans; Frans H Rutten; Arco Teske; Eric Boersma; Roxana Menken; Bas M van Dalen; Leonard Hofstra; Marianne Verhaar; Jasper Brugts; Folkert Asselbergs; Hester den Ruijter; Isabella Kardys

doi:10.1038/s41598-024-65667-0

Identifying plasma proteomic signatures from health to heart failure, across the ejection fraction spectrum

Karolina Andrzejczyk, Sabrina Abou Kamar, Anne-Mar van Ommen, Elisa Dal Canto, Teun B Petersen, Gideon Valstar, K Martijn Akkerhuis, Maarten Jan Cramer, Victor Umans, Frans H Rutten, Arco Teske, Eric Boersma, Roxana Menken, Bas M van Dalen, Leonard Hofstra, Marianne Verhaar, Jasper Brugts, Folkert Asselbergs, Hester den Ruijter, Isabella Kardys^*

^*Corresponding author for this work

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Abstract

Circulating proteins may provide insights into the varying biological mechanisms involved in heart failure (HF) with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). We aimed to identify specific proteomic patterns for HF, by comparing proteomic profiles across the ejection fraction spectrum. We investigated 4210 circulating proteins in 739 patients with normal (Stage A/Healthy) or elevated (Stage B) filling pressures, HFpEF, or ischemic HFrEF (iHFrEF). We found 2122 differentially expressed proteins between iHFrEF-Stage A/Healthy, 1462 between iHFrEF-HFpEF and 52 between HFpEF-Stage A/Healthy. Of these 52 proteins, 50 were also found in iHFrEF vs. Stage A/Healthy, leaving SLITRK6 and NELL2 expressed in lower levels only in HFpEF. Moreover, 108 proteins, linked to regulation of cell fate commitment, differed only between iHFrEF-HFpEF. Proteomics across the HF spectrum reveals overlap in differentially expressed proteins compared to stage A/Healthy. Multiple proteins are unique for distinguishing iHFrEF from HFpEF, supporting the capacity of proteomics to discern between these conditions.

Original language	English
Article number	14871
Number of pages	12
Journal	Scientific Reports
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41598-024-65667-0
Publication status	Published - 27 Jun 2024

Keywords

Biomarkers
HFpEF
HFrEF
Heart failure
Proteomics

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Andrzejczyk, K., Abou Kamar, S., van Ommen, A.-M., Canto, E. D., Petersen, T. B., Valstar, G., Akkerhuis, K. M., Cramer, M. J., Umans, V., Rutten, F. H., Teske, A., Boersma, E., Menken, R., van Dalen, B. M., Hofstra, L., Verhaar, M., Brugts, J., Asselbergs, F., den Ruijter, H., & Kardys, I. (2024). Identifying plasma proteomic signatures from health to heart failure, across the ejection fraction spectrum. Scientific Reports, 14(1), Article 14871. https://doi.org/10.1038/s41598-024-65667-0

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title = "Identifying plasma proteomic signatures from health to heart failure, across the ejection fraction spectrum",

abstract = "Circulating proteins may provide insights into the varying biological mechanisms involved in heart failure (HF) with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). We aimed to identify specific proteomic patterns for HF, by comparing proteomic profiles across the ejection fraction spectrum. We investigated 4210 circulating proteins in 739 patients with normal (Stage A/Healthy) or elevated (Stage B) filling pressures, HFpEF, or ischemic HFrEF (iHFrEF). We found 2122 differentially expressed proteins between iHFrEF-Stage A/Healthy, 1462 between iHFrEF-HFpEF and 52 between HFpEF-Stage A/Healthy. Of these 52 proteins, 50 were also found in iHFrEF vs. Stage A/Healthy, leaving SLITRK6 and NELL2 expressed in lower levels only in HFpEF. Moreover, 108 proteins, linked to regulation of cell fate commitment, differed only between iHFrEF-HFpEF. Proteomics across the HF spectrum reveals overlap in differentially expressed proteins compared to stage A/Healthy. Multiple proteins are unique for distinguishing iHFrEF from HFpEF, supporting the capacity of proteomics to discern between these conditions.",

keywords = "Biomarkers, HFpEF, HFrEF, Heart failure, Proteomics",

author = "Karolina Andrzejczyk and {Abou Kamar}, Sabrina and {van Ommen}, Anne-Mar and Canto, {Elisa Dal} and Petersen, {Teun B} and Gideon Valstar and Akkerhuis, {K Martijn} and Cramer, {Maarten Jan} and Victor Umans and Rutten, {Frans H} and Arco Teske and Eric Boersma and Roxana Menken and {van Dalen}, {Bas M} and Leonard Hofstra and Marianne Verhaar and Jasper Brugts and Folkert Asselbergs and {den Ruijter}, Hester and Isabella Kardys",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = jun,

day = "27",

doi = "10.1038/s41598-024-65667-0",

language = "English",

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Andrzejczyk, K, Abou Kamar, S, van Ommen, A-M, Canto, ED, Petersen, TB, Valstar, G, Akkerhuis, KM, Cramer, MJ, Umans, V, Rutten, FH, Teske, A, Boersma, E, Menken, R, van Dalen, BM, Hofstra, L, Verhaar, M, Brugts, J, Asselbergs, F , den Ruijter, H & Kardys, I 2024, 'Identifying plasma proteomic signatures from health to heart failure, across the ejection fraction spectrum', Scientific Reports, vol. 14, no. 1, 14871. https://doi.org/10.1038/s41598-024-65667-0

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T1 - Identifying plasma proteomic signatures from health to heart failure, across the ejection fraction spectrum

AU - Andrzejczyk, Karolina

AU - Abou Kamar, Sabrina

AU - van Ommen, Anne-Mar

AU - Canto, Elisa Dal

AU - Petersen, Teun B

AU - Valstar, Gideon

AU - Akkerhuis, K Martijn

AU - Cramer, Maarten Jan

AU - Umans, Victor

AU - Rutten, Frans H

AU - Teske, Arco

AU - Boersma, Eric

AU - Menken, Roxana

AU - van Dalen, Bas M

AU - Hofstra, Leonard

AU - Verhaar, Marianne

AU - Brugts, Jasper

AU - Asselbergs, Folkert

AU - den Ruijter, Hester

AU - Kardys, Isabella

PY - 2024/6/27

Y1 - 2024/6/27

N2 - Circulating proteins may provide insights into the varying biological mechanisms involved in heart failure (HF) with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). We aimed to identify specific proteomic patterns for HF, by comparing proteomic profiles across the ejection fraction spectrum. We investigated 4210 circulating proteins in 739 patients with normal (Stage A/Healthy) or elevated (Stage B) filling pressures, HFpEF, or ischemic HFrEF (iHFrEF). We found 2122 differentially expressed proteins between iHFrEF-Stage A/Healthy, 1462 between iHFrEF-HFpEF and 52 between HFpEF-Stage A/Healthy. Of these 52 proteins, 50 were also found in iHFrEF vs. Stage A/Healthy, leaving SLITRK6 and NELL2 expressed in lower levels only in HFpEF. Moreover, 108 proteins, linked to regulation of cell fate commitment, differed only between iHFrEF-HFpEF. Proteomics across the HF spectrum reveals overlap in differentially expressed proteins compared to stage A/Healthy. Multiple proteins are unique for distinguishing iHFrEF from HFpEF, supporting the capacity of proteomics to discern between these conditions.

AB - Circulating proteins may provide insights into the varying biological mechanisms involved in heart failure (HF) with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). We aimed to identify specific proteomic patterns for HF, by comparing proteomic profiles across the ejection fraction spectrum. We investigated 4210 circulating proteins in 739 patients with normal (Stage A/Healthy) or elevated (Stage B) filling pressures, HFpEF, or ischemic HFrEF (iHFrEF). We found 2122 differentially expressed proteins between iHFrEF-Stage A/Healthy, 1462 between iHFrEF-HFpEF and 52 between HFpEF-Stage A/Healthy. Of these 52 proteins, 50 were also found in iHFrEF vs. Stage A/Healthy, leaving SLITRK6 and NELL2 expressed in lower levels only in HFpEF. Moreover, 108 proteins, linked to regulation of cell fate commitment, differed only between iHFrEF-HFpEF. Proteomics across the HF spectrum reveals overlap in differentially expressed proteins compared to stage A/Healthy. Multiple proteins are unique for distinguishing iHFrEF from HFpEF, supporting the capacity of proteomics to discern between these conditions.

KW - Biomarkers

KW - HFpEF

KW - HFrEF

KW - Heart failure

KW - Proteomics

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U2 - 10.1038/s41598-024-65667-0

DO - 10.1038/s41598-024-65667-0

M3 - Article

C2 - 38937570

SN - 2045-2322

VL - 14

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 14871

ER -

Identifying plasma proteomic signatures from health to heart failure, across the ejection fraction spectrum

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