Activation of cell signaling mechanisms as a potential target of cardiac protection against ischemic injury

Activation of cell signaling mechanisms as a potential target of cardiac protection against ischemic injury.

 

Number of project: APVV-LPP-0393-09

Principal Investigator: Tatiana Ravingerová

 

Duration: 09/2009 – 09/2013

 

Annotation:

 

The project is focused on the investigation of endogenous defensive mechanisms in the myocardium and possibility to enhance its resistance to the main manifestations of acute ischemia (infarction, myocardial dysfunction and lethal arrhythmias) by means of cardiac adaptation to stress. The research will be aimed to characterize the mechanisms of cell signaling with particular regards to the role of phosphatidylinositol 3-kinase (PI3K)/Akt as a key enzyme system involved in antiapoptotic processes and metabolic regulations, as well as on the study of PI3K/Akt interaction with transcription factors (nuclear receptors PPAR). The role of activation of PI3K/Akt and PPAR in the mechanisms of cardiac ischemic tolerance will be investigated during short-term adaptive response (preconditioning) in the hearts of the healthy rats and diabetic animals exposed to acute myocardial ischemia or hypoxia. Using physiological, pharmacological and biochemical methods on the models in vitro the relationship of the above processes with generation of NO, free oxygen radicals and function of mitochondrial K(ATP) channels will be also studied. The obtained results may contribute to the elucidation of the pathophysiological mechanisms of ischemic injury in the healthy and diseased myocardium as well as to the development of new methods of its protection against ischemia that may be potentially utilized in the treatment of ischemic heart disease.