Differential Gene Expression und Nebivolol and Atenolol during Experimental Ischemia in Human Myocardium

Journal of Clinical and Basic Cardiology 2008; 11 (1-4): 16-23

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Keywords: Atenolol,  beta blocker,  gene expression,  ischaemia,  myocardium,  Nebivolol

Introduction: During and after myocardial ischemia, betablockers support the preservation of myocardial integrity. In the present study, nebivolol is compared with another standard betablocker, here atenolol, commonly used in the treatment of myocardial ischemia. In human preparations, we found remarkable differences in the expression profiles between nebivolol and atenolol, both during simulated myocardial ischemia and normoxia. Here we report on these noteworthy differences in expression profiles. Results: Our results show that, in particular, on the level of reverse transcription and T-cell-mediated immunity as well as in the process of angiogenesis, a noteworthy regulation is brought about by nebivolol. Similarly, biological processes involved in cell-mediated immunity and reverse transcription are significantly up-regulated by nebivolol and not by atenolol. Cell-mediated immunity is largely involved in tissue repair. In well-oxygenized preparations, we have shown that numerous biochemical processes, mainly those involved in signalling and cellular immunity, are affected by nebivolol but not by atenolol. This shows that, in non-ischemic, well-perfused preparations, nebivolol unfolds particular, possibly cardioprotective effects which cannot be observed under atenolol. Similarly, we can see that many processes involved in contraction, lipid metabolism, and proliferation are down-regulated by nebivolol only (not by atenolol). In well-oxygenized preparations, we found numerous biochemical processes up-regulated by nebivolol (not by atenolol): of special interest in this context are reverse transcription, stress response, and protein phosphorylation. It is interesting that nebivolol, but not atenolol, leads to a downregulation of gene expression in glutamine-glutamate conversion and pyruvate metabolism, the latter of particular interest in ischemia. In welloxygenized preparations, we can see that numerous biological pathways, mainly those involved in signalling, angiogenesis, cellular immunity, and EGF are affected by nebivolol but not by atenolol. Concerning nebivolol-regulated biological pathways, we could see that, during normoxia, upregulation of pathways is hardly pronounced by nebivolol over atenolol. From these data we can certainly deduce that nebivolol unfolds a large number of molecular actions not seen in atenolol. This is reflected in differential gene expression both in well-oxygenated and ischemic preparations.