Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Kasa, M.
The effects of the pan HDAC inhibitor Vorinostat on contractility and calcium cycling in murine ventricular cardiomyocytes
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2021. pp. 89
[OPEN ACCESS]
FullText
- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Rainer Peter
- Wallner Markus
- Altmetrics:
- Abstract:
- Introduction Heart failure (HF) with preserved ejection fraction (HFpEF) is an increasing worldwide health problem with no proven effective therapies, disproportionately affecting women and the elderly. It was previously shown that inhibition of histone deacytelase catalytic activity improves cardiac systolic and diastolic function in rodent and feline models of HFpEF via hyperacetylation of a variety of proteins. The specific mechanisms underlying enhanced cardiac function are not fully understood. The aim of this study was to assess the effects of suberanilohydroxamic acid (SAHA), a pan-HDAC inhibitor, on calcium cycling and sarcomere kinetics in murine ventricular cardiomyocytes. Methods Experiments were performed using ventricular cardiomyocytes (CM) isolated from healthy C57BL/6J mice (n=5). Freshly isolated murine CM were incubated with 5 µM SAHA (n=32) for 90 minutes and compared to vehicle treated CM (n=30). Sarcomere shortening and cytosolic calcium were measured using an epifluorescence microscope and calcium sensitive dyes while the cells were electrically stimulated. Results SAHA did not induce any changes in diastolic sarcomere length, shortening amplitude, or parameters of relaxation in murine CM, both at baseline and following exposure to the β - adrenergic agonist Isoproterenol. Furthermore, diastolic calcium levels, amplitude as well as RT10 and RT50 were unaffected by SAHA. Conclusions Current literature contains substantial evidence that SAHA treatment results in a significant improvement in both contraction and relaxation characteristics of feline (in-vivo) and rat (in vitro) CM. However, with the experiments conducted for this thesis, we were not able to detect any significant effect elicited by the short-term incubation of murine ventricular CM with the panHDACi Vorinostat.