Centre of Experimental Medicine SAS
Topic
Mechanisms underlying the cardioprotective effects of SGLT2 inhibitors in heart failure: an experimental basis for clinical benefits
PhD. program
Normal and pathological physiology
Year of admission
2026
Name of the supervisor
RNDr. Matúš Sýkora, PhD.
Contact:
Receiving school
Medical Faculty of Comenius University
Annotation
Heart failure represents one of the leading causes of hospitalization and mortality in cardiology, and despite
significant advances in therapy, it remains a condition with an unfavorable prognosis. In recent years, sodium glucose cotransporter 2 (SGLT2) inhibitors have demonstrated significant improvements in clinical outcomes in patients with heart failure, independently of the presence of diabetes mellitus. However, the mechanisms through which these agents exert their beneficial effects on myocardial structure and function have not yet been fully elucidated. The aim of this doctoral thesis is to contribute to the understanding of the molecular and cellular mechanisms underlying the cardioprotective effects of SGLT2 inhibitors in the setting of heart failure, with a particular focus on myocardial remodeling processes, especially alterations in the extracellular matrix and disturbances in intercellular communication, which play a key role in the development of systolic and diastolic dysfunction as well as arrhythmogenesis. An experimental rat model of an aortocaval fistula will be used, mimicking chronic volume overload and leading to the progressive development of heart failure comparable to clinical conditions in patients. The study will focus on the assessment of myocardial remodeling
in the left and right atria as well as in the left and right ventricles, with an emphasis on the expression and
distribution of selected proteins involved in intercellular communication and the structural integrity of the
myocardium. The results of this work may contribute to a better understanding of the biological mechanisms
by which SGLT2 inhibitors improve the clinical course of heart failure, thereby supporting their rational use in clinical practice. In addition, they may provide a basis for the identification of new therapeutic targets aimed at
preventing or reversing pathological myocardial remodeling.
significant advances in therapy, it remains a condition with an unfavorable prognosis. In recent years, sodium glucose cotransporter 2 (SGLT2) inhibitors have demonstrated significant improvements in clinical outcomes in patients with heart failure, independently of the presence of diabetes mellitus. However, the mechanisms through which these agents exert their beneficial effects on myocardial structure and function have not yet been fully elucidated. The aim of this doctoral thesis is to contribute to the understanding of the molecular and cellular mechanisms underlying the cardioprotective effects of SGLT2 inhibitors in the setting of heart failure, with a particular focus on myocardial remodeling processes, especially alterations in the extracellular matrix and disturbances in intercellular communication, which play a key role in the development of systolic and diastolic dysfunction as well as arrhythmogenesis. An experimental rat model of an aortocaval fistula will be used, mimicking chronic volume overload and leading to the progressive development of heart failure comparable to clinical conditions in patients. The study will focus on the assessment of myocardial remodeling
in the left and right atria as well as in the left and right ventricles, with an emphasis on the expression and
distribution of selected proteins involved in intercellular communication and the structural integrity of the
myocardium. The results of this work may contribute to a better understanding of the biological mechanisms
by which SGLT2 inhibitors improve the clinical course of heart failure, thereby supporting their rational use in clinical practice. In addition, they may provide a basis for the identification of new therapeutic targets aimed at
preventing or reversing pathological myocardial remodeling.