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

Journal of Clinical and Basic Cardiology

Tscheliessnigg KH¹  Gasser R¹  Trantina-Yates A¹  Brussee H¹  Porta S¹  Gasser S¹  Kraigher-Krainer E¹  Roessl U¹  Lewinski D¹  Mangge H¹  Scherr E¹  Friehs I¹  Mächler H¹  Ablasser K¹  Udermann H¹ 

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关键词: Atenolol;    beta blocker;    gene expression;    ischaemia;    myocardium;    Nebivolol;   

DOI  :  

学科分类：心脏病和心血管学

来源: Krause & Pachernegg GmbH

【 摘 要 】

Introduction: During and after myocardial ischemia, betablockers support the preservation of myocardial integrity. In the present study, nebivololis compared with another standard betablocker, here atenolol, commonly used in the treatment of myocardial ischemia. In human preparations, wefound 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 transcriptionand 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, wecan see that many processes involved in contraction, lipid metabolism, and proliferation are down-regulated by nebivolol only (not by atenolol). Inwell-oxygenized preparations, we found numerous biochemical processes up-regulated by nebivolol (not by atenolol): of special interest in thiscontext are reverse transcription, stress response, and protein phosphorylation. It is interesting that nebivolol, but not atenolol, leads to a downregulationof gene expression in glutamine-glutamate conversion and pyruvate metabolism, the latter of particular interest in ischemia. In welloxygenizedpreparations, we can see that numerous biological pathways, mainly those involved in signalling, angiogenesis, cellular immunity, andEGF are affected by nebivolol but not by atenolol. Concerning nebivolol-regulated biological pathways, we could see that, during normoxia, upregulationof 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.

【 授权许可】

Unknown