Regulated RIPK3 Necroptosis is Produced in Cardiovascular Tissues and Cells in Dietary Magnesium Deficiency: Roles of Cytokines and Their Potential Importance in Inflammation and Atherogenesis

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

“…3 Using transmission EM, and Mg-deficient animals (dietary deficiency for 21 days), and excised ventricular myocytes, peripheral and cerebral arterial cells, we noted that some of these cells demonstrated rupture of plasma membranes, swelling of cell organelles (i.e., mitochondria, Golgi, and ER), characteristic signs of necroptosis. 41 ELISA assays clearly demonstrated activation of RIPK3, thus proving necroptosis was activated in the diverse cardiac and arterial myocytes of the Mg-deficient animals. 41 Interestingly, treatment of the Mg-deficient animals with an inhibitor of RIPK3, viz., necrostatin -1 reduced the activation of NF-kB; NF-kB inhibition is known to reduce necroptosis.…”

“…41 ELISA assays clearly demonstrated activation of RIPK3, thus proving necroptosis was activated in the diverse cardiac and arterial myocytes of the Mg-deficient animals. 41 Interestingly, treatment of the Mg-deficient animals with an inhibitor of RIPK3, viz., necrostatin -1 reduced the activation of NF-kB; NF-kB inhibition is known to reduce necroptosis. Overall, our new data would suggest that activation of necroptosis probably plays an important role in inflammation and atherogenesis seen in experimentally-induced cardiac and vascular diseases.…”

“…4 Examination of cardiac and arterial myocytes from the 21-day Mg-deficient animals revealed that some of these myocytes showed these characteristic signs of pyroptosis. 43 Examination of coronary arterial tissues from patients undergoing bypass surgery in our hospitals revealed falls in serum ionized Mg and intracellular free Mg contents of red blood cells (Table 2), elevated serum IL-1beta, IL-18 and caspase-1, thus suggesting that many of the arterial cells underwent pyroptosis. 43,44 Scanning EM of several of the arterial muscle cells of these bypass patients showed distinct, characteristic signs of ruptured plasma membranes.…”

“…Upon close examination of the coronary and aortic arterial smooth muscle cells of the rats and rabbits fed low Mg diets, and using transmission EM, we noticed some strange morphological alterations akin to apoptosis, necroptosis, ferroptosis, and pyroptosis in different cells. [41][42][43][44]…”

Why typos in DNA may help to fuel atherogenesis and inflammation prior to heart attacks, ischemic heart disease, and sudden-death ischemic heart disease: roles of unrecognized ionized hypomagnesemia and epigenetics

“…118 Not surprisingly, using rats subjected to 21-days of Mg deficiency, we found that cardiovascular tissues and cells of these animals demonstrated 6-8x up-regulation of p53 along with growth arrest, cell senescence, apoptosis, and several forms of programmed CD (i.e.,apoptosis, necroptosis, pyroptosis, and ferroptosis). 91,100,104,[119][120][121][122] all events found in diverse forms of atherogenesis. 13,14 As stated above, we have found considerable evidence to prove that Mg deficiency induces oxidation of DNA, 11,12,91,100,123 fragmentation of DNA, histone alterations and methylation of the DNA all events clearly demonstrating epigenetic changes in the genomes of the Mg deficient cardiac and vascular smooth muscle cells.…”