[The gene expression signature in endothelial cells exposed to mitomycin C]. / Profil' gennoi ékspressii v éndotelial'nykh kletkakh, kul'tiviruemykh v prisutstvii mitomitsina S.

The expression of DNA repair (DDB1, ERCC4, ERCC5), leukocyte adhesion (VCAM1, ICAM1, SELE, SELP), endothelial mechanotransduction (KLF4), endothelial differentiation (PECAM1, CDH5, CD34, NOS3), endothelial-to-mesenchymal transition (SNAI1, SNAI2, TWIST1, GATA4, ZEB1, CDH2), scavenger receptors (LOX1, SCARF1, CD36, LDLR, VLDR), antioxidant system (PXDN, CAT, SOD1) and transcription factor (HEY2) genes in primary human coronary (HCAEC) and internal thoracic (HITAEC) arteries endothelial cells exposed to alkylating mutagen mitomycin C (MMC) was studied at two time points - after 6 h of incubation with MMC and after 6 h of the genotoxic load followed by 24 h of incubation in pure culture medium using the quantitative PCR. Immediately after MMC exposure, in the exposed HCAEC and HITAEC a decreased expression of almost all studied genes was noted excepted SNAI, which demonstrated a 4-told increase in its expression compared to the unexposed control. Elimination of MMC from the cultures, an increased expression of the VCAM1, ICAM1, SELE, SNAI2, KLF4 genes and a decreased the mRNA level of the PECAM1, CDH5, CD34, ZEB1, CAT, PXDN genes were observed in both cell lines. In addition, HITAEC cells were characterized by a decreased expression of the SOD1, SCARF1, CD36 genes and an increased expression of the SNAI1 and TWIST1 genes; in HCAEC, an increased mRNA level of the LDLR and VLDLR genes was noted. Thus, MMC-induced genotoxic stress is associated with the endothelial dysfunction.

[The expression level of cytokine genes in the cases of native heart valves in infectious endocarditis]. / Otsenka urovnia ékspressii genov tsitokinov v stvorkakh nativnykh klapanov serdtsa pri infektsionnom éndokardite.

The expression level of IL1B, IL6, IL8, IL10, IL12A, IL12B, IL18, IL23, IL33, CCL2, and IL1RL1 has been investigated using biopsies of native mitral, aortic, and tricuspid valves obtained during surgical correction of acquired defect from 25 patients with infectious endocarditis. Biopsies of native mitral and aortic valve cusps from 12 patients who underwent surgical correction of acquired heart disease of non-infectious etiology were used as control. We used quantitative PCR with fluorescent dye SYBR Green for determination of the cytokine gene expression level. This study revealed that genes could be subdivided into three groups: (i) genes with increased expression (IL1B, IL6, and IL8); (ii) genes with reduced expression (IL33 and IL1RL1); (iii) genes with unchanged expression (IL12A, IL18, IL23, and CCL2). The IL8 gene expression was characterized by the most pronounced increase (9.83 times versus control), while the IL1RL1 gene demonstrated the most pronounced decrease in its expression (4.17 times). Expression of IL10 and IL12B genes was negligible in all samples.

[Prospects of Application of Remote Preconditioning at Heart Revascularization].

Remote ischemic preconditioning of the heart exerts anti-necrotic, antiarrhythmic, inotropic effects that have been demonstrated in clinical trials in cardiac surgery both in adults and children. However, so far there is no consensus between cardiologists regarding the impact of remote preconditioning on the incidence of intraoperative myocardial infarctions and mortality in the postoperative period. Until now there is no unanimity concerning choice of remote preconditioning protocol and timing of its application before cardiac surgery.

Effects of Deltorphin II and Its Retroenantio Analog on Cardiac Tolerance to Ischemia and Reperfusion.

Selective agonist of δ2-opioid receptors deltorphin II and its retroenantio analog (0.12 mg/kg intravenously) were preventively injected to male Wistar rats 15 min prior to 45-min coronary occlusion or 5 min before 120-min reperfusion. Administration of deltorphin II before artery occlusion and before reperfusion decreased the infarct size/area at risk ratio. Deltorphin II prevented the appearance of ischemia-provoked ventricular arrhythmias and exerted no effect on HR and BP (systolic and diastolic). The retroenantio analog of deltorphin II produced no antiarrhythmic or infarct-limiting effects, but reduced HR without affecting BP. Deltorphin II can be viewed as a promising prototype for a medicinal remedy to treat acute myocardial infarction.

CB-Receptor Agonist HU-210 Mimics the Postconditioning Phenomenon of Isolated Heart.

CB receptor agonist HU-210 exhibits an infarction-limiting effect during in vitro reperfusion of the heart after focal ischemia. This effect is paralleled by a decrease in left-ventricular developed pressure and double product. In addition, HU-210 reduces end-diastolic pressure during the reperfusion period, which indirectly attests to reduced Ca2+ overload of cardiomyocytes.

[PHENOMENON OF REMOTE PRECONDITIONING THE HEART AND ITS MAIN MANIFESTATIONS].

Remote ischemic preconditioning prevents reperfusion cardiomyocyte apoptosis and has the infarct-limiting effect which is maintained in the experiments on the isolated perfused heart. Remote preconditioning promotes to recovery the contractility of the heart during reperfusion, but did not affect the incidence of occlusion and reperfusion of ventricular arrhythmias. Remote preconditioning has a mild anti-inflammatory effect. Presented article is a review and formulated conclusions based on the published literature data.

[PROBLEM OF END EFFECTOR OF ISCHEMIC PRECONDITIONING OF THE HEART].

An analysis of the literature data performed by the authors shows that the main contenders for the role of the end effector of ischemic preconditioning of the heart are: (1) MPT pore (2) nexuses (3) cytoskeleton. Thus, almost all of the known intracellular molecular cascades eventually converge on MPT pore, on the components of the cytoskeleton and nexuses.

[SIGNIFICANCE OF OPIOID RECEPTORS IN THE CYTOPROTECTIVE ACTION OF CHRONIC HYPOXIA DURING ANOXIA-REOXYGENATION OF CARDIOMYOCYTES].

It was investigated the role of δ-, µ- и κ-opioid receptors (ORs) in the development of cytoprotective effect of chronic normobaric hypoxia (CNH) using anoxia/reoxygenation of isolated cardiomyocytes. Adaptation to CNH was achieved by the maintenance of rats for 21 days at atmosphere containing 12% O2. Anoxia/reoxygenation of isolated cardiomyocytes of intact rats evoked a death of 23% cells and enhancement of lactate dehydrogenase (LDH) release from cells. Anoxia/reoxygenation of isolated cardiomyocytes of adapting rats induced a death of only 2.5% cells and LDH release decreased by 25%. Preliminary incubation of cells with the OR blocker naloxone (300 nM) or the δ-OR antagonist TIPP(ψ) (30 nM) or the selective δ2-OR antagonist naltriben (1 nM) or the µ-OR antagonist CTAP (100 nM) 25 min prior to anoxia abolished adaptive enhancement of cell survival and a decrease in LDH release. The blocking of δ1-OR by BNTX (1 nM) or κ-OR by nor-binaltorphimine (3 nM) not affected on the cytoprotection at CNH. Consequently, cardiac cell δ2- and µ-opioid receptors are involved in the cytoprotective effect of chronic normobaric hypoxia.

[CHRONIC CONTINUOUS NOR-MOBARIC HYPOXIA AUGMENTS CELL TOLERANCE TO ANOXIA(REOXYGE-NATION: THE ROLE OF PROTEIN KINASES].

The study evaluated the role of protein kinase C, PI3-kinase and tyrosine kinases in the cardi-oprotective effect of the chronic continuous normobaric hypoxia (CCNH). Adaptation to CCNH was provided by placing the rats in an atmosphere with a low content of O2 (12 %) during 21 days. Anoxia-reoxygenation of isolated cardiomyocytes of intact rats caused the deaths of 16.5 % of the cells and the lactate dehydrogenase (LDH) release of them. A similar effect on isolated cardiomyocytes of adapted rats caused the death of only 6.8 % of the cells and less pronounced increase in LDH release. Preincubation of cells for 25 minutes with one of the protein kinases inhibitors: che-lerythrine (10 |mM/l); rottlerin (1 |j.M/l); genistein (50 |mM/l) eliminated the adaptive increase in cell survival and reduction of LDH release. Incubation of cells with PI3-kinase blocker wortman-nin (100 nM/l) had no effect on the percentage of cell death of adapted animals and LDH release from them after anoxia-reoxygenation. The authors believe that the cytoprotective effect of chronic normobaric hypoxia is realized through activation of protein kinase C-5 and tyrosine kinases. Kinase PI3 - is not involved in the implementation of protective actions CCNH.

[CARDIOPROTRECTIVE EFFECT OF REMOTE POSTCONDITIONING: MECHANISMS AND POSSIBILITIES OF CLINICAL APPLICATION].

Experimental data indicate that postconditioning at a distance is an effective method for cardiac protection against reperfusion injury. Remote postconditioning prevents reperfusion necrosis and apoptosis of cardiomyocytes, decreases a probability of postinfarction remodeling of the heart. Cardioprotective effect of remote postconditioning depends on the release of tissue factor(s) increasing cardiac tolerance to long-term ischemia-reperfusion after transient ischemia. Clinical investigations show that postconditioning at a distance is an effective method for the prevention of reperfusion injury of the heart during coronary artery bypass surgery.

[Neuroprotective and nephroprotective effects of remote postconditioning: Prospects for clinical use]. / Neiroprotektornyi i nefroprotektornyi éffekty distantnogo prekonditsionirovaniia. Perspektivy klinicheskogo primeneniia.

The results of experimental and clinical studies strongly suggest that remote ischemic preconditioning (RIP) has no neuroprotective effect during cardiac surgery performed under extracorporeal circulation. Remote preconditioning (RP) has no neuroprotective effect in hemorrhagic stroke. A randomized multicenter study is needed to evaluate the efficiency RIP in patients with ischemic stroke. RP reduces the severity of ischemia/reperfusion kidney injury during transplantation. RIP has been established to prevent contrast-induced nephropathy. There is a need for a multicenter trial to evaluate the efficiency of RIP in patients with abdominal aortic aneurysm repair. Analysis of the presented data indicates that RIP fails to prevent cardiorenal syndrome in infants and children during cardiac surgery. The data available in the literature on the capacity of RIP to provide nephroprotective effect in patients after coronary artery bypass surgery are discordant and indicative of the advisability of a multicenter study.

[Remote preconditioning phenomenon. prospects for use in pathology of lung and gastrointestinal tract].

The literature data on the effectiveness of remote ischemic preconditioning (RIP) in the prevention of lung injury are contradictory. Authors of some works argue that RIP prevents lung damage during surgical interventions, the authors of other publications claim that the RIP does not protect lung against pathological processes. It is obvious that there is an urgent need for multicenter, randomized trials aimed at studying RIP protective effects against pathological processes in lung. Also required is clinical evaluation of the effectiveness of RIP in the thromboembolism of pulmonary arteries, the transplantation of the lungs and intestinal infarction. Remote preconditioning prevents the intestine injury associated with abdominal aortic aneurysm repair. Experimental data indicate that RIP has the hepatoprotective effect during ischemia and reperfusion injury of liver, septic or haemorrhagic shock. The question of whether the DIP has a protective effect during ischemia-reperfusion of the pancreas remains open.