PP.30.25] EFFECT OF MAGNESIUM DEPRIVATION ON HYPERTENSION RELATED GENE EXPRESSION PROFILES IN HUMAN HEART

Abstract

Objective: While we well understand that nutritional Mg2+-deprivation may lead to increased blood pressure and numerous cellular dysfunctions, the effects of extracellular Mg2+-concentrations on molecular pathways and processes has not been studied as yet. Characterising these Mg2+-dependent intracellular molecular pathways may well constitute a further step towards understanding the effects of magnesium on myocardial function as well as blood pressure control. Design and method: Using molecular profiling technique, we look at over to 20 000 different gene expressions in the presence and absence of extracellular Mg2+, thus identifying the specific molecular signature of myocardial Mg2+-deprivation. This allows us to demonstrate its effects at the molecular level in resting human atrial myocardium. Using PANTHER software (Applied Biosystems) we assess up- and down-regulation of gene expression associated with biological processes and pathways. Results: Myocardial gene expression after exposure of 30 minutes to Mg2+-free solution is massively altered compared to control experiments. We find a complex de-regulation of gene expression secondary to Mg2+ deficiency, several accociated with hypertension-related genes. It can be seen that gene-expression associated with clusters of immunity- and defence-processes, protein metabolism and signal transduction as well as nucleoside, nucleotide and nucleic metabolism are significantly down-regulated. Similarly, biological processes involved in transcription, protein biosynthesis and cell communication, nucleoside, nucleotide and nucleic metabolism as well as signal transduction and protein metabolism are effected by up-regulation. Clusters of pathways down-regulated by Mg2+ deficiency are: various signalling pathways, T-cell activation, apoptosis and angiogenesis. Clusters of up-regulated pathways are mainly different groups of signalling. Conclusions: In summary, experimental myocardial Mg2+-deprivation leads to complex changes in the expression profile of biological processes and molecular pathways. Furthermore, one can deduce from earlier observations that Mg2+i is well buffered and remains relatively uninfluenced by extracellular manoeuvres. The interdependence of intracellular and extracellular Mg2+, however, appears once more difficult to understand, but may well effect the development of arterial hypertension. Further studies are certainly needed in order to firmly establish the mechanisms of extracellular Mg2+ influencing intracellular processes and pathways that may affect blood pressure and myocardial function.