PhD Scientific Days 2023

Translational Medicine - Posters P

Proteomic Alterations in Left Ventricular Myocardium are Characteristically different in Chronic Heart failure induced by Pressure and Volume Overload

Text of the abstract

Introduction: Chronic pressure (PO) and volume (VO) overload are known to induce various changes in the left ventricular (LV) myocardium at the level of function and structure. However, there are no data in the literature about the proteomic alterations underlying the different heart failure (HF) phenotypes.
Aims: Hence, the aim of this study was to identify on LV myocardial samples from small animal models the proteomic alterations that underly the distinct HF phenotypes induced by PO and VO.
Methods: Transverse aortic constriction (TAC) method was used to induce PO. While, the VO was achieved by creating an aortocaval fistula (ACF). Age-matched sham-operated animals served as controls. Comparing the two HF models we used pressure-volume analysis, echocardiography, histology and quantitative real-time PCR. The expression pattern of myocardial proteins was determined by bottom-up exploratory proteomic analysis, followed by differential expression and gene ontology enrichment analysis (GO:BP).
Results: Advanced HF was successfully induced as a result of PO and VO. In the TAC group, massive wall thickening, concentric LV hypertrophy (LVH), marked interstitial fibrosis and diastolic dysfunction developed. However, the animals with VO-induced HF were characterized by LV dilatation, eccentric LVH, moderate fibrosis, and greatly reduced LV contractility. The high-throughput proteomic analysis identified 4691 proteins. Of these, 1404 and 913 have shown upregulation, while 1359 and 886 downregulation in the TAC and ACF groups compared to their corresponding control groups. GO:BP analysis revealed the downregulation of mitochondrial organization as well as the upregulation of actin cytoskeleton organization in the PO-induced HF animals. In addition, a robust downregulation of fatty acid oxidation and upregulation of endocytosis, defense and immune response was observed in the ACF group.
Conclusion: In our study, we observed that PO and VO-induced end-stage HF have different LV proteomic patterns beyond the distinct functional and structural remodeling known so far. This alteration at the proteomic level supports the need for etiology-based individualized therapy.
Funding:
NKFIH K134939 (to T.R. MD, PhD);
TKP2021-EGA-23;
RRF-2.3.1-21-2022-00003_NKL_VMKL