Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Walter, A.
Autophagiemarker in Herzinsuffizienz unterschiedlicher Ätiologie
Humanmedizin; [ Diplomarbeit ] Medizinische Universität Graz; 2022. pp. 74
[OPEN ACCESS]
FullText
- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Holzer Senka
- Wallner Markus
- Altmetrics:
- Abstract:
- Introduction: In eukaryotic cell homeostasis, autophagy is an important physiological mechanism to process cellular debris in order to disassemble and recycle them. There are different autophagy mechanisms digesting different cargo, and they are dependent on various regulatory mechanism. Especially postmitotic cells are dependent on autophagy, for they are unable to regenerate by mitosis. Like in cardiomyocytes, intact autophagy machinery is crucial for normal cardiac function. Beside that physiological importance, autophagy is also relevant in pathophysiological context. Both excessively upregulated or downregulated autophagic activity is harmful. In this thesis, macroautophagy and mitophagy will be investigated for alteration of autophagy markers in human and rat hearts with different etiologies of heart failure. Method: For this purpose, 7 weeks old male Dahl salt-sensitive rats were set on different diets. To induce cardiac remodelling, a subgroup was fed an 8% NaCl high-salt diet (HSD) and for control, a subgroup was fed a 0.3% low-salt diet (LSD). In vivo phenotyping with blood pressure measurements was performed at two-weeks intervals, and the LSD group and a portion of the HSD group (early stage of cardiac remodelling) were sacrificed after 5 weeks of diet to collect left ventricular heart tissue. The remaining rats on HSD further continued their diet for 5 weeks (late stage of cardiac remodelling) and the procedure was repeated. For investigation of human samples, the clinical department for cardiosurgery of the Medical University of Graz provided left ventricular heart tissue selected from non-failing hearts to serve as control, and to compare from hearts with diastolic dysfunction and dilated cardiomyopathy (DCM). For whole tissue cell homogenates of human and rat left ventricular myocardium, immunoblotting was performed to investigate markers of heart failure (NCX1, SERCA2a), autophagy-related proteins (p62, Atg5, LC3B, Parkin, Pink1) and the autophagy-regulator mTOR. Results: In the rat model, we could show that in the late stage of cardiac remodelling, there was a significant increase in LC3B and Parkin. Changes in the other autophagy-related proteins failed to reach significance. In the human samples of diastolic dysfunction, no significant findings were made. Those were only achieved in patients with DCM, there was a significant increase in both mTOR and p-mTOR levels. Discussion: For hypertensive Dahl salt-sensitive rats, we expected downregulation of autophagy with regard to other data. Our results confirmed that only in partial. To clarify the ambiguous and unchanged results, further investigations and methods are necessary. This also applies for the data obtained in human samples. Also, an expansion of sample size could help to show the anticipated results, since some results already showed trends but without extend for significance.