Proteomics

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Protein profiling of plasma samples of patients with dilated cardiomyopathy and differences according to the disease prognosis


ABSTRACT: Dilated cardiomyopathy (DCM) is a disease of the heart muscle characterized by left ventricular or biventricular dilation and systolic dysfunction. It presents one of the most common causes of heart failure worldwide and also the most common indication for heart transplantation. Despite the discharge treatment possibilities, the outcome of patients with recent onset DCM often remains unpredictable and major adverse events may occur in the first months following the diagnosis. Enhancement in the left ventricular ejection fraction – designed as the left ventricular reverse remodeling (LVRR) – has been considered one of the most important determinants of the improvement and treatment response in the prognosis of DCM. In the present study we performed a comprehensive quantitative proteomic analysis of DCM patients’ plasma samples. First we searched for the differences against healthy control group and found several proteins and biological processes to be significantly regulated. The most DCM up-regulated terms corresponded to inflammatory response, wound healing and complement. Among the most relevant DCM up-regulated proteins were CRP, CD163, AOC3, PF4, IGF2, IGFBP2 and TNC. Down-regulation in DCM samples was observed in the biological processes of blood coagulation and lipid metabolism, both of which present risk factors in cardiovascular diseases. The most relevant down-regulated proteins in DCM were TTN, GSN, FCN3, PON1, PON3, and COMP. In the second part of the study, we observed the clinical fate of the DCM patients one year after admission. We divided them according to their treatment response into subgroups of responders (LVRR+) and non-responders (LVRR-) and searched for proteins that would help to predict the patient’s fate or to elucidate the molecular consequences of the disease progression. The protein with the best prognostic potential was ALDOB, its elevated plasma level was found in patients with worse or fatal outcome. The patients with no or poor treatment response had also up-regulated immunoglobulins and pathways corresponding to immunoglobulin-mediated immune response together with cell adhesion which points to the importance of these processes in the DCM pathology.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

DISEASE(S): Cardiovascular System Disease

SUBMITTER: Jana Klimentova  

LAB HEAD: Jiří Stulík

PROVIDER: PXD046288 | Pride | 2024-02-19

REPOSITORIES: Pride

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Publications

Proteomic Profiling of Dilated Cardiomyopathy Plasma Samples ─ Searching for Biomarkers with Potential to Predict the Outcome of Therapy.

Klimentova Jana J   Rehulka Pavel P   Stulik Jiri J   Vozandychova Vera V   Rehulkova Helena H   Jurcova Ivana I   Lazarova Marie M   Aiglova Renata R   Dokoupil Jiri J   Hrecko Juraj J   Pudil Radek R  

Journal of proteome research 20240216 3


Determination of the prognosis and treatment outcomes of dilated cardiomyopathy is a serious problem due to the lack of valid specific protein markers. Using in-depth proteome discovery analysis, we compared 49 plasma samples from patients suffering from dilated cardiomyopathy with plasma samples from their healthy counterparts. In total, we identified 97 proteins exhibiting statistically significant dysregulation in diseased plasma samples. The functional enrichment analysis of differentially e  ...[more]

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