|Gasser R et al.|
Immunological Implications in Experimental Myocardial Ischaemia: MPO (Myeloperoxidase) Expression Is Differentially Regulated by Beta-Blockers, While CD80 Expression Remains Unaffected
Journal of Clinical and Basic Cardiology 2011; 14 (1-4): 16-22
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Keywords: CD80, myeloperoxydase, myocardial ischaemia
In this article, we present some examples of differential gene expression between nebivolol and atenolol. However, from these data we can certainly deduce that beta-blockers unfold a large number of molecular actions. This is reflected in a particular molecular signature, a differential gene expression both in well-oxygenated and ischaemic preparations. In earlier publications, we identified a specific molecular signature of myocardial ischaemia, which possibly equals the severity and type of tissue damage produced – on the other hand, it may demonstrate the activation of repair mechanisms and changes in the metabolic state of the cell. In the presence and absence of beta-blockers, we have seen that numerous intracellular pathways and processes during ischaemia are affected, which are related to ischaemia and cardio-protection. Using PCR for validation, we find that, during experimental ischaemia, there is an upregulation of MPO expression. There is a differential regulation between different beta-blockers during myocardial ischaemia, which warrants further investigation. We believe that there are complex pleiotropic effects of beta-blockers on T-cell immunity. Such pleiotropic effects have recently received more attention. For example, in the JUPITER trial, in apparently healthy persons without hyperlipidaemia but with elevated high-sensitivity Creactive protein levels, rosuvastatin significantly reduced the incidence of major cardiovascular events by unfolding pleiotropic anti-inflammatory actions. Our preliminary results show that beta-blockers inhibit the expression of T-cell immunity-related genes during experimental hypoxia. However, a further detailed exploration on both expression and molecular levels is certainly needed. Using PCR, we also tested for CD80: it can be seen that during experimental ischaemia, there is an up-regulation of CD80 expression, however, not statistically significant. There is also a regulation with and without the influence of beta-blockers during myocardial ischaemia. The main message we believe to have taken so far from our investigations is that the most important, unique pleiotropic effects of beta-blockers may be centred around favourable effects upon the immunological response to ischaemia as well as around cardio-protection. Future clinical studies shall investigate the specific immunological significance of these molecular pathways within the framework of cardio-protection.