Proteins linked to atherosclerosis and cell proliferation are associated with the shrunken pore syndrome in heart failure patients

Liana Xhakollari; Amra Jujic; John Molvin; Peter Nilsson; Hannes Holm; Erasmus Bachus; Margret Leosdottir; Anders Grubb; Anders Christensson; Martin Magnusson

doi:10.1002/prca.202000089

Proteins linked to atherosclerosis and cell proliferation are associated with the shrunken pore syndrome in heart failure patients

Liana Xhakollari, Amra Jujic, John Molvin, Peter Nilsson, Hannes Holm, Erasmus Bachus, Margret Leosdottir, Anders Grubb, Anders Christensson, Martin Magnusson

Research output: Contribution to journal › Article › peer-review

Abstract

PURPOSE: The "Shrunken pore syndrome" (SPS) is characterized by a difference in renal filtration between cystatin C and creatinine, resulting in a low eGFRcystatinC /eGFRcreatinine -ratio. Studies have demonstrated a high risk for cardiovascular morbidity and mortality for patients with SPS. In this discovery study, we explored associations between SPS and proteins implicated in cardiovascular disease and inflammation in patients with heart failure.

EXPERIMENTAL DESIGN: Plasma samples from 300 individuals in HARVEST-Malmö trial hospitalized for the diagnosis of heart failure (mean age 74.9±11.5 years; 30.0% female), were analyzed with a proximity extension assay consisting of 92 proteins. A Bonferroni-corrected p-value of 0.05/92 = 5.4 × 10-4 was considered significant in the initial age and sex-adjusted analyses. Presence of SPS was defined as eGFRcystatinC ≤60% of eGFRcreatinine .

RESULTS: SPS presented with significant associations (p < 5.4 × 10-4 ) in age and sex-adjusted logistic regressions with elevated levels of six proteins; scavenger receptor cysteine rich type 1 protein M130, tumor necrosis factor receptor 1, tumor necrosis factor receptor 2, osteoprotegerin, interleukin-2 receptor subunit alpha, and tyrosine-protein kinase receptor UFO. All proteins remained associated (p < 0.05) with SPS after multivariate adjustments.

CONCLUSIONS AND CLINICAL RELEVANCE: In heart failure patients, SPS was associated with proteins linked to atherosclerosis and cell proliferation. This article is protected by copyright. All rights reserved.

Original language	English
Article number	2000089
Journal	Proteomics Clinical Applications
Volume	15
Issue number	4
Early online date	2021 Mar 7
DOIs	https://doi.org/10.1002/prca.202000089
Publication status	Published - 2021

Subject classification (UKÄ)

Cardiology and Cardiovascular Disease

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/prca.202000089

1 Doctoral Thesis (compilation)

The cardiorenal syndrome: Structural and functional aspects including associations with the shrunken pore syndrome
Xhakollari, L., 2021, Lund: Lund University, Faculty of Medicine. 68 p.
Research output: Thesis › Doctoral Thesis (compilation)

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Xhakollari, L., Jujic, A., Molvin, J., Nilsson, P., Holm, H., Bachus, E., Leosdottir, M., Grubb, A., Christensson, A., & Magnusson, M. (2021). Proteins linked to atherosclerosis and cell proliferation are associated with the shrunken pore syndrome in heart failure patients. Proteomics Clinical Applications, 15(4), Article 2000089. https://doi.org/10.1002/prca.202000089

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author = "Liana Xhakollari and Amra Jujic and John Molvin and Peter Nilsson and Hannes Holm and Erasmus Bachus and Margret Leosdottir and Anders Grubb and Anders Christensson and Martin Magnusson",

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AU - Xhakollari, Liana

AU - Jujic, Amra

AU - Molvin, John

AU - Nilsson, Peter

AU - Holm, Hannes

AU - Bachus, Erasmus

AU - Leosdottir, Margret

AU - Grubb, Anders

AU - Christensson, Anders

AU - Magnusson, Martin

PY - 2021

Y1 - 2021

N2 - PURPOSE: The "Shrunken pore syndrome" (SPS) is characterized by a difference in renal filtration between cystatin C and creatinine, resulting in a low eGFRcystatinC /eGFRcreatinine -ratio. Studies have demonstrated a high risk for cardiovascular morbidity and mortality for patients with SPS. In this discovery study, we explored associations between SPS and proteins implicated in cardiovascular disease and inflammation in patients with heart failure.EXPERIMENTAL DESIGN: Plasma samples from 300 individuals in HARVEST-Malmö trial hospitalized for the diagnosis of heart failure (mean age 74.9±11.5 years; 30.0% female), were analyzed with a proximity extension assay consisting of 92 proteins. A Bonferroni-corrected p-value of 0.05/92 = 5.4 × 10-4 was considered significant in the initial age and sex-adjusted analyses. Presence of SPS was defined as eGFRcystatinC ≤60% of eGFRcreatinine .RESULTS: SPS presented with significant associations (p < 5.4 × 10-4 ) in age and sex-adjusted logistic regressions with elevated levels of six proteins; scavenger receptor cysteine rich type 1 protein M130, tumor necrosis factor receptor 1, tumor necrosis factor receptor 2, osteoprotegerin, interleukin-2 receptor subunit alpha, and tyrosine-protein kinase receptor UFO. All proteins remained associated (p < 0.05) with SPS after multivariate adjustments.CONCLUSIONS AND CLINICAL RELEVANCE: In heart failure patients, SPS was associated with proteins linked to atherosclerosis and cell proliferation. This article is protected by copyright. All rights reserved.

AB - PURPOSE: The "Shrunken pore syndrome" (SPS) is characterized by a difference in renal filtration between cystatin C and creatinine, resulting in a low eGFRcystatinC /eGFRcreatinine -ratio. Studies have demonstrated a high risk for cardiovascular morbidity and mortality for patients with SPS. In this discovery study, we explored associations between SPS and proteins implicated in cardiovascular disease and inflammation in patients with heart failure.EXPERIMENTAL DESIGN: Plasma samples from 300 individuals in HARVEST-Malmö trial hospitalized for the diagnosis of heart failure (mean age 74.9±11.5 years; 30.0% female), were analyzed with a proximity extension assay consisting of 92 proteins. A Bonferroni-corrected p-value of 0.05/92 = 5.4 × 10-4 was considered significant in the initial age and sex-adjusted analyses. Presence of SPS was defined as eGFRcystatinC ≤60% of eGFRcreatinine .RESULTS: SPS presented with significant associations (p < 5.4 × 10-4 ) in age and sex-adjusted logistic regressions with elevated levels of six proteins; scavenger receptor cysteine rich type 1 protein M130, tumor necrosis factor receptor 1, tumor necrosis factor receptor 2, osteoprotegerin, interleukin-2 receptor subunit alpha, and tyrosine-protein kinase receptor UFO. All proteins remained associated (p < 0.05) with SPS after multivariate adjustments.CONCLUSIONS AND CLINICAL RELEVANCE: In heart failure patients, SPS was associated with proteins linked to atherosclerosis and cell proliferation. This article is protected by copyright. All rights reserved.

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DO - 10.1002/prca.202000089

M3 - Article

C2 - 33682349

SN - 1862-8354

VL - 15

JO - Proteomics Clinical Applications

JF - Proteomics Clinical Applications

IS - 4

M1 - 2000089

ER -

Proteins linked to atherosclerosis and cell proliferation are associated with the shrunken pore syndrome in heart failure patients

Abstract

Subject classification (UKÄ)

UN SDGs

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Research output

The cardiorenal syndrome: Structural and functional aspects including associations with the shrunken pore syndrome

Cite this