Magnesium: Forgotten mineral in cardiovascular biology and atherogenesis

Abstract

In this review, a rationale is presented for how hypercholesterolemia, hypertension, diabetes mellitus (DM), end-stage renal disease (ESRD), prolonged stress, and exposure to magnesium (Mg)-wasting drugs can lead to atherosclerosis, ischemic heart disease, and stroke. The data, accumulated so far, indicate that Mg deficiency caused either by a poor diet or errors in Mg metabolism may be a missing link between diverse cardiovascular risk factors and atherogenesis. Early data from our laboratory and others indicate that reduction in extracellular free Mg ions can induce an entire array of pathophysiological phenomena known to be important in atherogenesis, that is, vasospasm, hypoxia, increased vascular reactivity, and elevation in intracellular calcium (Ca). More recent data has demonstrated molecular events, pointing the way to atherogenesis: that is, formation of pro-inflammatory agents, generation of free radicals, platelet aggregation, modulation of macrophage and leukocyte mobility, and emigration across the endothelial wall. Finally, oxidation of lipoproteins, changes in membrane fatty acid saturation, changes in membrane plasmalogens, and N-phospholipids suggest alterations in intracellular lipid signals. It has been shown that Mg deficiency can modulate membrane sphingomyelinase, generate vasoactive and pathogenic sphingolipids, which could alter multiple intracellular signaling pathways, modulate transcription factors, and thus cause intimal plaque formation. © 2007 Springer-Verlag London Limited.