Book of Abstracts - New Frontiers 2022

Abstracts of poster presentations

THE CARDIOPROTECTIVE EFFECT OF REMOTE ISCHEMIC PRECONDITIONING AND PROTECTIVE SIGNALING PATHWAYS IN AGING RATS

L. Kindernay , M. Pilchová, M. Jelemenský, K. Ferenczyová, T. Ravingerová

Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovakia

The effect of age on the reduced tolerance to ischemia-reperfusion (I/R) injury and myocardial adaptative mechanisms has been demonstrated in several studies in human and also in animal hearts. However, the onset of this unfavorable phenotype and cellular mechanisms behind are less known. Nevertheless, some studies are controversial and show that cardioprotection was preserved even in older age. Currently, one of the most actively studied forms of cardioprotection is remote-ischemic preconditioning (RIPC), mainly for its possible clinical use. In many studies, a positive effect of RIPC has already been found in elderly patients. However, little is known about the effect of RIPC and its molecular basis in elderly animals. Therefore, our work focuses on clarifying the effect of RIPC on the resistance of the heart against I/R injury and on identifying proteins involved in protective pathways of RIPC in aging 13 months old rats. In Langendorff-perfused hearts exposed to 30-min I/120-min R without or with prior RIPC. RIPC (3 cycles of 5-min I/5-min R) was applied on the hind limb of anesthetized rats (pressure cuff inflation (200 mmHg)/deflation). We measured infarct size (IS), susceptibility to ventricular arrhythmias and recovery of contractile function (left ventricular developed pressure - LVDP). In parallel groups, left ventricle tissue was sampled for the detection of protein levels of RISK pathway and pro/anti-apoptotic cascades (Western blot analysis). Remote preconditioning provided the adaptation of the heart to conditions occurring during reperfusion of the ischemic heart, thereby improving its response to the development of lethal I/R injury. Myocardial infarct size decreased and LVDP recovery was improved after I/R, although there was no change in incidence of reperfusion arrhythmias. Positive effect of RIPC was also associated with increased phosphorylation of glycogen synthase kinase 3 beta (GSK3β) and expression of endothelial nitric oxide synthase (eNOS). However, increasing age is likely to have caused a premature increase in protein kinase B (Akt) phosphorylation, that's why following RIPC could no more result in its increase. By induction of RIPC, the expression of proteinkinase C epsilon (PKCε) did not alter, while the apoptotic activity of t he myocardial cells was decreased (Bax/Bcl-2 ratio). As a result, the application of RIPC provided protection of the heart against I/R injury to some degree in the 13 months old rats. Therefore, even at this age, RIPC appears to be still an effective and clinically easy-to-use form of cardioprotection.

Keywords: ischemia-reperfusion injury, preconditioning, protective cell signaling, aging

Funding: APVV-16-0263, APVV-19-0540, VEGA 2/0141/18

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