PhD. Topics
Centre of Experimental Medicine SAS
Topic
Sex-specific effects of incretin-based therapy on myocardial ischemia–reperfusion injury in aged diabetic rats
PhD. program
Biochemistry
Year of admission
2026
Name of the supervisor
Mgr. Kristína Ferenczyová, PhD.
Contact:
Receiving school
Faculty of Natural Sciences Comenius University
Annotation
Over the past decades, substantial progress has been made in the investigation of mechanisms underlying myocardial injury and its pharmacological modulation; nevertheless, cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality, particularly in the ageing population with concomitant metabolic comorbidities. Advanced age, type 2 diabetes mellitus (T2DM), and obesity markedly modify the myocardial response to ischemic injury and limit the effectiveness of many experimentally validated therapeutic approaches in clinical practice. In this context, modern antidiabetic and anti-obesity agents, particularly incretin-based therapies, have gained increasing attention, as they exert not only metabolic effects but also beneficial actions on the cardiovascular system. However, their translational potential needs to be verified in experimental models that realistically reflect the clinical setting, including advanced age, multiple comorbidities, and biological sex differences. The aim of this doctoral thesis is to comprehensively characterize the effects of state-of-the-art antidiabetic and anti-obesity drugs in experimental models of myocardial ischemia–reperfusion injury, acute myocardial infarction, and chronic heart failure in adult and ageing diabetic rats with associated metabolic disorders (T2DM), with a particular focus on sex-specific differences. The project will be designed as a multidisciplinary study encompassing the assessment of cardiovascular function, including detailed analyses of hemodynamic, electrophysiological, and vascular parameters, complemented by the evaluation of biochemical and molecular markers related to myocardial remodeling, inflammation, oxidative stress, and cell death. The methodological approach will combine advanced surgical procedures with in vivo and in vitro techniques, including Western blot analyses and other molecular and biochemical methods.
The experimental models employed incorporate key characteristics of real-world patients in whom ischemic myocardial injury most frequently occurs, namely advanced age, the presence of metabolic comorbidities, and biological sex differences. This approach enables a more realistic evaluation of the therapeutic potential of the investigated drugs and increases the likelihood of successful translation of experimental findings into the clinical setting. The expected results may substantially contribute to a deeper understanding of the mechanisms of cardiometabolic injury in the context of ageing and sex differences, and provide a foundation for the development of more targeted and effective therapeutic strategies.
The experimental models employed incorporate key characteristics of real-world patients in whom ischemic myocardial injury most frequently occurs, namely advanced age, the presence of metabolic comorbidities, and biological sex differences. This approach enables a more realistic evaluation of the therapeutic potential of the investigated drugs and increases the likelihood of successful translation of experimental findings into the clinical setting. The expected results may substantially contribute to a deeper understanding of the mechanisms of cardiometabolic injury in the context of ageing and sex differences, and provide a foundation for the development of more targeted and effective therapeutic strategies.