CEEPC/IPM/CMSC - Abstrakt prezentace

(CEEPC/IPM/CMSC 2022 - ThS-05)
Novel circulating biomarkers of biventricular heart failure

Matěj Běhounek 1 *, Denisa Lipcseyová 1, Lucie Hrdá 1, Vojtěch Melenovský 2, Jan Beneš 2, Jiří Petrák 1

  1. First Faculty of Medicine Charles University, BIOCEV
  2. Institute for Clinical and Experimental Medicine (IKEM), Prague

Abstrakt

Chronic heart failure is characterized by insufficient supply of blood to body organs. Heart failure typically affects left ventricle (LVHF), in some patients the dysfunction may also affect the right ventricle, leading to biventricular heart failure (BiVHF). BiVHF patients have worse prognosis and respond differently to therapies. The molecular mechanisms responsible for HF are still poorly understood and reliable diagnostic markers distinguishing BiVHF from LVHF are missing.The aim of the study is to identify proteins differentially expressed in BiVHF compared to LVHF. We are interested in proteins whose differential expression in heart would be reflected in patient plasma, proteins that could serve as diagnostic biomarkers. We performed LFQ proteomic analysis of human hearts solubilized by Triton X100 to get rid of a large part of the myofibril proteins. The proteomic analysis of both ventricles from 10 LVHF, 10 BiVHF patients and 10 healthy donors identified roughly 3000 proteins. Among the differentially expressed were proteins associated with myofibril, cell adhesion and extracellular matrix, cell metabolism, calcium homeostasis, endothelial cell repair and protein degradation. We confirmed differential expression of APOA4, AHSG, FBLN5, HMGCS2, MFAP4, and UCHL1 by western blots, and tested whether their abundance in circulation reflects the differential expression in the heart tissue. ELISA showed significantly decreased plasma concentration of APOA4 in both types of HF compared to healthy individuals and confirmed significantly elevated concentrations of fibulin-5 (FBLN5) in BiVHF patients compared to healthy controls. These putative circulating markers of general HF and BiVHF, respectively, will be tested for their specificity and selectivity in a larger study.

* Korespondující autor: matej.behounek@lf1.cuni.cz


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