Thesis topic proposal
Péter Bencsik
The ischemic adaptation of the myocardium Subtopic: The role of matrix metalloproteinase-2 in ischemic heart injury


Institute: University of Szeged
theoretical medicine
Graduate School of Multidisciplinar Medical Scienses

Thesis supervisor: Péter Bencsik
Location of studies (in Hungarian): Univ. Szeged, Fac. of Medicine, Dept. of Biochemistry
Abbreviation of location of studies: ÁOK

Description of the research topic:

Ischemic heart disease and its consequence, chronic heart failure are the leading causes of death in several countries of the European Union including Hungary. The treatment of ischemic heart disease is based on more different mechanisms, however, it is still not completely accomplished.
The mission of the Cardiovascular Research Group, Department of Biochemistry, Faculty of Medicine, University of Szeged is to investigate the possible ways of the treatment of cardiovascular diseases and their risk factors such as hyperlipidemia, diabetes and uremia. As the head of the in vivo laboratory of the research group, my objective is to find procedures and/or medications in rodent models, which can be suitable for the treatment of ischemic heart disease and heart failure.
Recently, researches have focused on matrix metalloproteinases (MMP) due to their role in the development and progression of cardiovascular diseases. MMPs are zinc-dependent endopeptidases playing role in the degradation and re-building of extracellular proteins, thereby they contribute to physiological processes such as embryogenesis and wound healing. It is already known that MMPs may play a crucial role in inflammatory diseases, carcinogenesis or tumour metastases, and in the remodeling of different tissues following their hypoxic/ischemic injury. It has been shown that MMP-2 expresses even in the intracellular space of isolated cardiomyocytes, therefore it is plausibly involved in signalling and/or metabolic processes. Furthermore, our research group previously showed myocardial activation of MMP-2 during ischemia/reperfusion injury, which can be attenuated by conditioning of the heart. Moreover, it has been also described that activated MMP-2 plays a pivotal role in the progression of ischemic heart failure via myocardial remodeling.
Therefore, my research objective is to investigate the expression and activity of MMP-2 in the development and progression of myocardial ischemia/reperfusion injury and heart failure int he presence or absence of risk states. Further aim is to examine the functional/morphological changes after pharmacological inhibition of MMP-2 in the above-mentioned disease models, and preclinical application of MMP-2 inhibitors in cardiovascular diseases focusing on ischemia/reperfusion injury and heart failure.
I would flash on some of our routinely applied models and methods such as the rodent models of myocardial infarction or heart failure induced by transient or permanent coronary occlusion, respectively. In addition, our research group possesses well-established models of hyperlipidemia and uremia induced by 5/6 nephrectomy in rats. A high performance ultrasound unit and a pressure-volume catheter system are available for the in vivo functional and morphological analysis of the heart and there is an arsenal of biochemical and molecular measurements proceeded with great experience and high quality.

Required language skills: English
Number of students who can be accepted: 1

Deadline for application: 2017-07-15

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