Book of Abstracts - New Frontiers 2022

Abstracts of oral presentations

LEFT VENTRICLE REMODELLATION IN ZUCKER DIABETIC FATTY RATS BUT ALSO IN ZUCKER LEAN RATS

M. Kollárová 1,2 , M. Chomová 3 , D. Radošinská 4 , Ľ. Tóthová 5 , J. Radošinská 1,6

1 Institute of Physiology, Faculty of Medicine, Comenius University, Bratislava, Slovakia; 2 Premedix Academy, Bratislava, Slovakia; 3 Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of Medicine, Comenius University, Bratislava, Slovakia; 4 Institute of Immunology, Faculty of Medicine, Comenius University, Bratislava, Slovakia; 5 Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University. Bratislava, Slovakia; 6 Centre of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences; Bratislava, Slovakia The Zucker diabetic fatty (ZDF) rat is a widely used animal model of type 2 diabetes mellitus (DM2) that represents a major risk factor for cardiovascular diseases. In the pathogenesis of DM2, matrix metalloproteinases (MMPs) play a significant role. MMPs are proteolytic enzymes involved in the degradation and remodelling of the extracellular matrix that can serve as possible predictors of the treatment effectiveness or the development of DM2 complications. The hyperglycaemia generates oxidative stress in DM2 that promotes MMP activation. The aim of our study was to observe biometric and biochemical parameters and MMP activities in plasma and myocardial tissue of ZDF rats and compare them with two possible controls. We worked with males of 3 rat strains: ZDF inbred rats (n=16), Wistar outbred (WIS, independent control, n=14), and Zucker Lean (LEAN, control, n=15). Body weight, blood glucose, plasma insulin and lipid levels of all experimental animals were recorded. Based on fasting glycaemia and insulin concentrations, ZDF rats were split into 2 phenotypes - obese (FAT) and diabetic (DIA). Markers of oxidative stress, antioxidant capacity, and carbonyl stress were analysed spectrophotometrically and fluorometrically in plasma, left and right ventricle. The activity of MMP-2 and MMP-9 was determined by gelatin zymography. FAT revealed stronger left ventricular hypertrophy and greater body weight, differentiating them fromDIA. Oxidative stress and antioxidant status pointed to higher oxidative stress in ZDF rats, both DIA and FAT. MMP-2 activity measured in plasma samples was lower in FAT compared with DIA (p=0.037) and it was also lower in DIA (p=0.011) and FAT (p<0.0001) compared with LEAN. MMP-9 activity was higher in WIS compared with LEAN (p=0.009) and higher in DIA compared with FAT (p<0.005) and LEAN (p<0.0001). In the right ventricle, the activity of MMP-2 was higher in LEAN compared with WIS (p=0.049). Similarly, in the left ventricle, the activity of MMP-2 was higher in LEAN compared with WIS (p=0.034). MMP-2 was higher in DIA (p=0.034), and FAT (p=0.008) compared with LEAN. Based on our study, the general characteristic of ZDF rats - hyperphagia, obesity, hyperinsulinemia, and insulin resistance, applies only to a part of ZDFs. Obese rats with a genetic load for diabetes, that have not yet developed severe hyperglycaemia, have lower plasma activity of MMP-2 and MMP-9 compared with rats assigned to a group characterized by hyperglycaemia and lower insulin levels. However, increased myocardial MMP-2 activity indicates left ventricular remodelling in both ZDF phenotypes. The greater left ventricular weight, increase in carbonyl stress in the left myocardial tissue and the increase in MMP-2 activity in both ventricles of LEAN, could indicate myocardial remodelling in comparison with WIS. The inhomogeneity of ZDF rats may be beneficial in the study of different aspects of this pathology.

Keywords: diabetes mellitus, hyperglycaemia, gelatinases, oxidative stress, heart

Funding:This research was funded by the Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic grant No. VEGA 1/0314/19 and VEGA 1/0193/21, and grant for young researchers of Comenius University in Bratislava UK/78/2021.

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