Our laboratory is addressing three of the most important issues in vascular biology today: stroke mechanisms; roles of chemical and immune factors in atherogenesis; and molecular mechanisms of sudden-death ischemic heart diseases. These ongoing studies have already led to the prevention of atherosclerotic lesions, hypertensive vascular diseases, stroke-like events, and the sequelae of lethal events in diverse forms of circulatory shock and septicemia in diverse animal models. Other studies have led to the discovery of a brand-new protein immune factor which we have termed HDFx. Our ongoing studies indicate that this new stimulatory factor can also enhance wound healing and prevent death induced by several lethal bacterial and fungal agents.
We have found that magnesium-deficient states underlie many vascular disease processes and release/synthesize sphingolipids, platelet-activating factor(PAF), cytokines, chemokines, and a variety of cell-death factors from vascular smooth muscle cells, endothelial cells, and cardiac muscle cells. In addition, we have found, at least experimentally in animal models, that HDFx can ameliorate, often, the lethal actions of hemorrhage, trauma, septic shock, liver cancers, and most-likely, several types of hemorrhagic fever viruses.
For these ongoing- studies, we utilize NMR spectroscopy, in-vivo high-resolution TV microscopy, digital-image microscopy, confocal laser scanning microscopy, culture of primary vascular and cardiac muscle cells, ion-selective electrodes, ELISA assays, poly- and monoclonal antibodies, and lipid chemistry.
Turlapaty, P. D. M. V., and Altura, B. M. (1980). Magnesium deficiency produces spasms of coronary arteries: Relationship to etiology of sudden death ischemic heart disease. Science 208, 198-200.
Altura, B. M., Altura, B. T., and Carella, A. (1983). Magnesium deficiency-induced spasms of umbilical vessels: relation to preeclampsia, hypertension, growth retardation. Science 221, 376-378.
Altura, B. M., Altura, B. T., Gebrewold, A., Ising, H., and Gunther, T. (1984). Magnesium deficiency and hypertension:Correlation between magnesium-deficient diets and microcirculatory changes in situ. Science 223, 1315-1317.
Zhang, A., Cheng, T. P.-O., and Altura, B. M. (1992). Magnesium regulates intracellular free ionized calcium concentration and cell geometry in vascular smooth muscle cells. Biochim. Biophys. Acta 1134, 25-29.
Resnick, L. M., Altura, B. T., Gupta, R. K., Laragh, J. H., Alderman, M. H., and Altura, B. M. (1993). Intracellular and extracellular magnesium depletion in type 2 (non-insulin) dependent diabetes mellitus. Diabetologia 36, 767-770.
Morrill, G. A., Gupta, R. K., Kostellow, A. B., Ma, G. Y., Zhang , A., Altura, B. T., and Altura, B. M. (1997). Mg2+ modulates membrane lipids in vascular smooth muscle: Link to atherogenesis. FEBS Lett. 408, 191-194.
Altura, B. M., Kostellow, A. B., Zhang, A., Li, W., Morrill, G. A., Gupta, R. K., and Altura, B. T. (2003). Expression of the nuclear factor-kB and proto-oncogenes c-fos and c-jun are induced by low extracellular Mg2+ in aortic and cerebral vascular smooth muscle cells: Possible links to hypertension, atherogenesis, and stroke. Am. J. Hypert. 16, 701-707.
Altura, B. M., Shah, N. C., Shah, G., Zhang, A., Li, W., Zheng, T., Perez-Albela, J. L., and Altura, B. T. (2012). Short-term magnesium deficiency upregulates ceramide synthase in cardiovascular tissues and cells: cross-talk among cytokines, Mg2+, NF-KB, and de novo ceramide. Am. J. Physiol. Heart Circ. Physiol. 302, H319-H332.
Altura, B. M., Gebrewold, A., Carella, A. (2016). HDFx: A recently discovered biologic and its potential use in prevention and treatment of hemorrhagic fever viruses and antibiotic-resistant superbugs. J. Hematol. Thromboembolic. Dis. 4, 100252.
Altura, B. M., Gebrewold, A., Carella, A., and Altura, B. T. (2016). HDFx: A potential new treatment and prophylactic agent against nonalcoholic steatohepatitis (NASH) and subsequent hepatocellular carcinomas: Is hypomagnesemia a complication of the disease? J. Alcoholism Drug. Depend. 4, 1000e133.
Wenyan Li, Ph.D., Research Associate
Zhi-wei Yang, M.D., Ph.D., Research Associate
Ad Hoc Reviewer, NIH, NSF, and USDA study sections
Reviewer for various journals and funding organizations