Centre of Experimental Medicine SAS
Topic
Molecular and cellular mechanisms underlying the cardioprotective effects of SGLT2 inhibitors in an experimental model of heart failure
PhD. program
Animal physiology
Year of admission
2026
Name of the supervisor
RNDr. Matúš Sýkora, PhD.
Contact:
Receiving school
Faculty of Natural Sciences Comenius University
Annotation
Heart failure represents a serious clinical problem associated with high morbidity and mortality, and its pathogenesis involves complex molecular and cellular changes within the myocardium. Sodium–glucose cotransporter 2 (SGLT2) inhibitors have demonstrated significant cardioprotective effects independent of their hypoglycemic action; however, the precise mechanisms of their effects at the myocardial level are not yet fully elucidated. The aim of this doctoral thesis is to investigate the molecular and cellular mechanisms underlying the cardioprotective effects of SGLT2 inhibitors in an experimental model of heart failure, with a particular focus on alterations in the extracellular matrix and intercellular communication. A rat model of aortocaval fistula will be employed as the experimental model, leading to volume overload and the development of progressive heart
failure. The study will primarily focus on the assessment of extracellular matrix remodeling and the expression
of selected proteins involved in intercellular communication, which play a key role in the electrical and mechanical synchronization of the myocardium. The results of this study are expected to contribute to a better understanding of the mechanisms by which SGLT2 inhibitors modulate myocardial structure and function under conditions of heart failure and may provide a basis for the identification of novel therapeutic targets.
failure. The study will primarily focus on the assessment of extracellular matrix remodeling and the expression
of selected proteins involved in intercellular communication, which play a key role in the electrical and mechanical synchronization of the myocardium. The results of this study are expected to contribute to a better understanding of the mechanisms by which SGLT2 inhibitors modulate myocardial structure and function under conditions of heart failure and may provide a basis for the identification of novel therapeutic targets.