Cell death signaling mechanisms in cardiac failure caused by magnesium deficiency: relationship to etiology of atherogenesis and sudden death ischemic heart disease

Abstract

| http://medcraveonline.com deficiency (MgD) may be an underlying major factor via its direct actions on coronary and cerebral arterial and arteriolar blood vessels. 8-18 Over the past 40 years, numerous investigators have found evidence to support our hypothesis. 19-25 Originally, we thought the major reason for death from MI, IHD, and SDIHD was a greater and greater coronary and cerebral arteriolar and arterial vasoconstriction, thus reducing nutrition and oxygenation of the coronary and cerebral micro vasculatures. 10,12-16,17,26 However, our research over the past 40 years, in conjunction with the work of other investigators, has made this original, simple idea much more complicated. Below, we review how the original idea of arteriolar and arterial vasoconstriction sets into motion (i.e., triggers) a massive series of molecular and cellular pathways leading to the diverse forms of programmed cell death and autophagy mentioned above. Mg deficiency puts the squeeze on coronary and cerebral blood vessels An early report from our laboratories suggested a progressive dietary and/or metabolic-induced loss of Mg during early developmental stages of life, particularly in coronary arteries could lead to coronary arterial vasospasm (CAV), ischemic heart disease (IHD), and suddendeath ischemic heart disease (SDIHD). 11,12 Autopsy-driven results from children who died due to accidental causes have been reported which show early signs of atherogenesis (i.e., fatty streaks on the walls of the aorta and carotid arteries) in young children as early as six years of age. 27 Approximately 30 years ago, two of us using newly-developed selective ion-electrodes to measure blood, plasma and serum ionized Mg tested on some 35 cardiac patients presenting with Prinzmetal angina found, on average, a 35-40% decrease in the ionized Mg blood fraction with almost no change in the total Mg fraction; 28-30 cellular Mg 2+ measured with 31 P-nuclear magnetic resonance spectroscopy fell in parallel to the fall in serum ionized Mg (Table 1). What is very important about these results is that ever since Dr. William Heberden's findings in 1768, it has been known that Prinzmetal angina is a result of coronary arterial vasospasm. 31 So, it is very difficult to not associate our clinical findings on these cardiac patients with anything but coronary arterial vasospasm. Moreover, we have reported that when coronary arterial vessels are placed in contact with low concentrations of Mg 2+ , they go into intense vasospasm; the lower the Mg 2+ concentration, the greater the vasospasm. 11,12 Moreover, in the presence of circulating neurohumoral agents (e.g., norepinephrine, angiotensin II, numerous vasoactive peptides), the coronary arterial spasms become larger (obviously being potentiated