PhD Scientific Days 2023

Budapest, 22-23 June 2023

Translational Medicine - Posters P

Lasso-based feature selection identifies active relaxation as the most informative left ventricular parameter for proteomic perturbations during myocardial remodeling and reverse-remodeling

Bálint András Barta1, Mihály Ruppert1, Niko Pinter2, Eva Brombacher3, Clemens Kreutz3, Sevil Korkmaz-Icöz4, Attila Oláh1, Alex Ali Sayour1, Sylvia Spiesshofer1, Gábor Balázs Szabó5, Oliver Schilling2, Béla Merkely1, Tamás Radovits1
1 Scientific Research Laboratory, Heart and Vascular Center, Faculty of Medicine, Semmelweis University, Budapest
2 Institute of Surgical Pathology, Faculty of Medicine, University of Freiburg Medical Center, Freiburg
3 Institute of Medical Biometry and Statistics, Faculty of Medicine, University of Freiburg Medical Center, Freiburg
4 Department of Cardiac Surgery, University of Heidelberg, Heidelberg
5 Department of Cardiac Surgery, University Hospital Halle, Halle (Saale)

Text of the abstract

Introduction: Pressure overload (PO) leads to myocardial remodeling to the detriment of left ventricular (LV) function, while the effective use of pressure unloading therapies may induce reverse-remodeling and recovery of LV dynamics.
Aims: We set out to identify parameters of LV function, that show the closest relation to alterations of the myocardial proteome in various stages of myocardial remodeling and reverse-remodeling.
Methods: LV-PO was induced in male and female rats by aortic banding (AB, n=12). Sham-operated animals served as controls (Co, n=5). Pressure unloading was performed by debanding of the aorta at week 6 in some of the once AB rats (DB, n=5). Morphologic and functional aspects of LV remodeling were detected by echocardiography and pressure-volume analysis at week 6 and week 12. LV samples were prepared for high throughput LC-MS/MS explorative proteomics. Bioinformatic feature selection based on Lasso regularization was applied to find LV parameters closely related to the myocardial proteome.
Results: Among the 3343 proteins identified and quantified in our study, 416 proteins have shown significant association with changes in Tau (parameter of LV active relaxation) due to myocardial remodeling in the AB and to reverse-remodeling in the DB groups. Gene ontology biological process (GO:BP) analysis of above 416 proteins has indicated the role of epigenetic, post-transcriptional and post-translational regulatory processes. The altered regulation of protein expression affected processes related to cardiac structure and function, such as “regulation of cation channel activity” and “regulation of ion transmembrane transporter activity”, “cardiac muscle tissue development”.
Conclusion: We propose that parameters of LV active relaxation may be the best measures to assess the extent of myocardial reverse-remodeling after pressure unloading in experimental as well as clinical studies.
Funding: ÚNKP-22-3-II-SE-30