Immunological Implications in Experimental Myocardial Ischaemia: MPO (Myeloperoxidase) Expression Is Differentially Regulated by Beta-Blockers, While CD80 Expression Remains Unaffected

[摘要] In this article, we present some examples of differential gene expression between nebivolol and atenolol. However, from these data we can certainlydeduce that beta-blockers unfold a large number of molecular actions. This is reflected in a particular molecular signature, a differential geneexpression 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 tissuedamage 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 upregulationof MPO expression. There is a differential regulation between different beta-blockers during myocardial ischaemia, which warrantsfurther investigation.We believe that there are complex pleiotropic effects of beta-blockers on T-cell immunity. Such pleiotropic effects have recently received moreattention. For example, in the JUPITER trial, in apparently healthy persons without hyperlipidaemia but with elevated high-sensitivity Creactiveprotein levels, rosuvastatin significantly reduced the incidence of major cardiovascular events by unfolding pleiotropic anti-inflammatoryactions. 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 canbe seen that during experimental ischaemia, there is an up-regulation of CD80 expression, however, not statistically significant. There is also aregulation 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-blockersmay be centred around favourable effects upon the immunological response to ischaemia as well as around cardio-protection. Future clinical studiesshall investigate the specific immunological significance of these molecular pathways within the framework of cardio-protection.

[学科分类] 心脏病和心血管学

[关键词] CD80;myeloperoxydase;myocardial ischaemia