Book of Abstracts - New Frontiers 2022

Abstracts of oral presentations

RIP3 MEDIATES NECROPTOSIS AND NON-NECROPTOTIC INFLAMMATORY RESPONSE: AN INTERESTING PHARMACOLOGICAL TOOL FOR TREATMENT OF HEART DISEASES

A. Adameova

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University in Bratislava, Slovakia; Centre of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovakia Necroptosis has been identified in various cardiac diseases, however, very little is known about its underlying mechanisms. In addition to a canonical pathway involving RIP1-RIP3-MLKL axis, other molecules being associated with mitochondrial dynamics and function as well as oxidative stress have been proposed to be the signaling upstreams of RIP3. This protein kinase has also emerged as a convergence point of multiple signaling cascade involving non-necroptotic inflammation. Thus, RIP3 can be considered as an interesting and powerful pharmacological target. The approaches leading directly or indirectly to the lowering activity of RIP3 can possess remarkable cardioprotection due to the mitigation of various phenotypes of cardiac damage. The presentation will provide an experimental evidence of necroptosis activation in acute and subacute models of myocardial ischemia/reperfusion injury as well as in various failing hearts and highlight a role of active RIP3 in the pathomechanisms of such injuries. Finally, RIP3 released from the damaged heart will also be discussed with respect to its diagnostic and prognostic potential.

Keywords: RIP3, necroptosis, heart, ischemia, inflammation

Funding: APVV-20-0242, APVV-19-0540, APVV-15-0607, VEGA 1/0016/20, 2/0141/18

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