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pmid:36980219

Proteomic Analysis in Valvular Cardiomyopathy: Aortic Regurgitation vs. Aortic Stenosis.

Theresa Holst · Johannes Petersen · Sabine Ameling · Lisa Müller · Torsten Christ · Naomi Gedeon · Thomas Eschenhagen · Hermann Reichenspurner · Elke Hammer · Evaldas Girdauskas

Cells · 2023 doi:10.3390/cells12060878

Paper

complete

Experiment

complete

Data

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Analysis

partial

Execution

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Proteomic Analysis in Valvular Cardiomyopathy: Aortic Regurgitation vs. Aortic Stenosis.
doi
10.3390/cells12060878
pmid
36980219
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[0]
Theresa Holst
[1]
Johannes Petersen
[2]
Sabine Ameling
[3]
Lisa Müller
[4]
Torsten Christ
[5]
Naomi Gedeon
[6]
Thomas Eschenhagen
[7]
Hermann Reichenspurner
[8]
Elke Hammer
[9]
Evaldas Girdauskas
journal
Cells
year
2023
abstract
Left ventricular (LV) reverse remodeling after aortic valve (AV) surgery is less predictable in chronic aortic regurgitation (AR) than in aortic stenosis (AS). We aimed to disclose specific LV myocardial protein signatures possibly contributing to differential disease progression. Global protein profiling of LV myocardial samples excised from the subaortic interventricular septum in patients with isolated AR or AS undergoing AV surgery was performed using liquid chromatography-electrospray ionization-tandem mass spectrometry. Based on label-free quantitation protein intensities, a logistic regression model was calculated and adjusted for age, sex and protein concentration. Web-based functional enrichment analyses of phenotype-associated proteins were performed utilizing g:Profiler and STRING. Data are available via ProteomeXchange with identifier PXD039662. Lysates from 38 patients, including 25 AR and 13 AS samples, were analyzed. AR patients presented with significantly larger LV diameters and volumes (end-diastolic diameter: 61 (12) vs. 48 (13) mm, p < 0.001; end-diastolic volume: 180.0 (74.6) vs. 92.3 (78.4), p = 0.001). A total of 171 proteins were associated with patient phenotype: 117 were positively associated with AR and the enrichment of intracellular compartment proteins (i.e., assigned to carbohydrate and nucleotide metabolism, protein biosynthesis and the proteasome) was detected. Additionally, 54 were positively associated with AS and the enrichment of extracellular compartment proteins (i.e., assigned to the immune and hematopoietic system) was observed. In summary, functional enrichment analysis revealed specific AR- and AS-associated signatures of LV myocardial proteins.
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Consideration of age, sex and protein concentration as covariates led to a stepwise reduction in data variance. Hence, the logistic regression model was adjusted accordingly and used to identify proteins showing associations with patient classification (as defined by Odds ratio (OR, i.e., the chance to be assigned to the AR or AS group when protein intensity is high) and p < 0.075).
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Consideration of age, sex and protein concentration as covariates led to a stepwise reduction in data variance. Hence, the logistic regression model was adjusted accordingly and used to identify proteins showing associations with patient classification (as defined by Odds ratio (OR, i.e., the chance to be assigned to the AR or AS group when protein intensity is high) and p < 0.075).
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A total of 171 proteins were associated with patient phenotype: 117 were positively associated with AR and the enrichment of intracellular compartment proteins (i.e., assigned to carbohydrate and nucleotide metabolism, protein biosynthesis and the proteasome) was detected. Additionally, 54 were positively associated with AS and the enrichment of extracellular compartment proteins (i.e., assigned to the immune and hematopoietic system) was observed.
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Protein profiling of left ventricular tissue of patients with aortic valve disease
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Consideration of age, sex and protein concentration as covariates led to a stepwise reduction in data variance. Hence, the logistic regression model was adjusted accordingly and used to identify proteins showing associations with patient classification (as defined by Odds ratio (OR, i.e., the chance to be assigned to the AR or AS group when protein intensity is high) and p < 0.075).
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Proteomic Analysis in Valvular Cardiomyopathy: Aortic
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