Key achievements and results of the laboratory

 

Study of the myocardial ischemia/reperfusion injury mechanisms and development of the new techniques for diagnosis and experimental treatment of myocardial ischemia occupy a central position in the research activity of the Laboratory. Cardioprotective efficacy of different types of myocardial preconditioning, including local and remote ischemic preconditioning, pharmacological and metabolic preconditioning and preconditioning by physical factors was shown in a series of experiments performed in 2007—2010. In addition, antiarrhythmic effects of myocardial ischemic postconditioning were first demonstrated.

In recent years, researchers of the Laboratory of Myocardial Metabolism in collaboration with colleagues from the Laboratory of Nanotechnology have proved the concept of targeted delivery of the cardioprotective drugs into ischemic myocardium. The team have obtained and published data on the possibility of passive targeted delivery of adenosine in rats with myocardial ischemia/reperfusion using silica nanoparticles. Currently, there is an ongoing study of the effects of targeted drug delivery using nanoparticles with optimized profile of biodistribution and biodegradation, in particular polyorganosiloxane.

Researchers of the Laboratory together with the colleagues of the Institute of Molecular Biology and Genetics (A.V. Fedorov, K.A. Kondratov) performed the study of biomarker and regulatory roles of miRNAs in ischemia/reperfusion. It was shown that levels of several cardiac-specific miRNAs in blood plasma correlates well with the degree of myocardial injury detected by measurement of infarct size and troponin I levels. These studies suggest that miRNAs may be highly sensitive biomarkers of the myocardial ischemia/necrosis, and that is possible to develop the diagnostic kits for the detection of myocardial injury based on miRNAs.

Studies performed in the frame of the Grant of the Ministry of Education and Science of the Russian Federation in collaboration with the University Hospital “Carl Gustav Carus” of the Dresden University of Technology (Dresden, Germany), were aimed at investigation of the role of asymmetric dimethylarginine in the pathogenesis of myocardial ischemia/reperfusion injury in animal model of type 1 diabetes mellitus. Investigations on cardioprotection in diabetes mellitus were conducted in collaboration with the Institute of Endocrinology (E.N. Kravchuk). It was shown that AMP-activated protein kinase plays the key role in the mechanisms of the cardioprotective effects of metformin and metabolic preconditioning.

Priority data on the effects of different protocols of ischemic postconditioning on the neuronal viability of hippocampus and cerebral cortex, as well as on the cytoplasmic activity of key enzymes of energetic metabolism (lactate dehydrogenase, succinate dehydrogenase) were obtained in the study of endogenous neuroprotective mechanisms. Currently, these investigations are supported by the Grant of the Russian Foundation for Basic Research (Project “Study of Cytoprotective Mechanisms of Ischemic Pre- and Postconditioning Effects on Hippocampal and Neocortical Neurons in Global Cerebral Ischemia/Reperfusion Injury”).