Magnesium Deficiency, Sphingolipids, and Telomerase: Relevance to Atherogenesis, Cardiovascular Diseases, and Aging

Altura, Burton M.; Shah, Nilank C; Shah, Gatha J; Altura, Bella T.; Preedy, Victor R.; Patel, Vinood B.

doi:10.1007/978-3-319-40007-5_113-1

Cited by 3 publications

(11 citation statements)

References 114 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Collectively, these studies showed that coronary, renal and cerebral blood vessels underwent contraction and reduced blood flows when stimulated with a variety of ceramides. In addition, we found that a number of the ceramides and other sphingolipids resulted in increased membrane transport of Mg 2+ , increased membrane permeability, and inflammatory responses in cerebral, intestinal and skeletal muscle microvascular beds ( [78,95], unpublished findings). When all these physiological actions of the ceramides, sphingolipids and phospholipids are taken into consideration, one must conclude that low dietary Mg intake and/or errors in Mg metabolism could underlie the observed detrimental cardiac, renal and cerebral effects of T2D.…”

Section: Low Mg 2+ Induces Formation and Release Of Ceramides And Platelet-activating Factor (Paf) In Vascular Muscle Cells: Potential Rementioning

confidence: 94%

“…However, on closer examination of our early 31P-NMRS and proton-NMRS data, we noted a synthesis and release of PAF and PAFrelated lipids when vascular smooth muscle cells were exposed to low Mg 2+ [71,74,75,78]. Further examination of responses of intact and isolated blood vessels revealed that these PAF molecules produced different degrees of contraction and increased permeability in the intestinal, skeletal muscle, and cerebral microvasculatures ( [71,78], unpublished findings).…”

Section: Low Mg 2+ Induces Formation and Release Of Ceramides And Platelet-activating Factor (Paf) In Vascular Muscle Cells: Potential Rementioning

confidence: 97%

“…In the early 1990's, working with 31P-NMRS and Proton-NMRS (1H-NMRS), and isolated vascular smooth muscle cells, we noted that low [Mg 2+ ] 0 induced formation of a variety of sphingolipids and phospholipids [74,75]. We found that several of the sphingolipids, particularly ceramides, exert potent contractile effects on arterial and arteriolar blood vessels, including those in the heart, brain and periphery [76][77][78]. In addition, in the rat brain, using direct in-vivo quantitative video microscopy (at magnifications > 6,000x), we found that several of the ceramides induced potent venular vasoconstriction followed by adhesion (sticking) of leukocytes, macrophages and monocytes to the postcapillary venular walls leading to petechial hemorrhages and transudation of blood-formed elements into the brain perivascular tissues, similar to a hemorrhagic stroke [76,78].…”

Section: Low Extracellular Levels Of Mg 2+ Lead To Synthesis and Release Of Sphingolipids And Phospholipids In Vascular Smooth Muscle Celmentioning

confidence: 99%

“…Membrane transport of cations require Mg 2+ [20,48,85]. Examination of vascular and cardiac muscle exposed to low Mg 2+ revealed, to us, for the first time that all enzymes involved in the synthesis and release of ceramides, surprisingly, were up-regulated both in in-vitro and in-vivo [78,79,[86][87][88][89][90]. These Mg-deficient environments also resulted in increased levels of sphingosine, sphingosine-1-phosphate, Diacylglycerol (DAG), and diverse PKC isozymes [54,55,57,78,79,91].…”

Section: Low Mg 2+ Induces Formation and Release Of Ceramides And Platelet-activating Factor (Paf) In Vascular Muscle Cells: Potential Rementioning

confidence: 99%

“…Our labs, using intact animals and isolated blood vessels reported that, depending upon vessel type, and vascular tone, the sphingolipids resulted in contraction (and reduced blood flows) or sometimes vasodilation [57,[75][76][77][78][91][92][93][94]. Collectively, these studies showed that coronary, renal and cerebral blood vessels underwent contraction and reduced blood flows when stimulated with a variety of ceramides.…”

Section: Low Mg 2+ Induces Formation and Release Of Ceramides And Platelet-activating Factor (Paf) In Vascular Muscle Cells: Potential Rementioning

confidence: 99%

See 4 more Smart Citations

Why there is an Increased Risk of Cardiac Failure, Widening of Pulse Pressure and Hemorrhagic Stroke in Type 2 Diabetics Over Age 60: Roles of Unrecognized Hypomagnesemia and Epigenetics Coupled with Increased Levels of Ceramides, Cytokines, ROS, 4-HNE and Platelet-Activating Factor

Bm¹,

Carella²,

Gebrewold³

et al. 2020

J Clin Case Stu

View full text Add to dashboard Cite

However, despite more than 80 years of intensive research, it remains to be determined how this angiopathy and widened PP develop. The lack of highly sophisticated in-vivo, non-invasive biophysical and biochemical techniques which are needed to diagnose, early, the microvascular structural and hemorheological alterations in the heart and brain, unfortunately, has often missed the potential underlying changes which can lead to cardiac failure and/or stroke in people over 60 years of age. About seven in 10 people over 65 with diabetes will die of heart disease and one in six from a stroke.

show abstract

Section: Low Mg 2+ Induces Formation and Release Of Ceramides And Platelet-activating Factor (Paf) In Vascular Muscle Cells: Potential Rementioning

confidence: 94%

Section: Low Mg 2+ Induces Formation and Release Of Ceramides And Platelet-activating Factor (Paf) In Vascular Muscle Cells: Potential Rementioning

confidence: 97%

Section: Low Extracellular Levels Of Mg 2+ Lead To Synthesis and Release Of Sphingolipids And Phospholipids In Vascular Smooth Muscle Celmentioning

confidence: 99%

Section: Low Mg 2+ Induces Formation and Release Of Ceramides And Platelet-activating Factor (Paf) In Vascular Muscle Cells: Potential Rementioning

confidence: 99%

Section: Low Mg 2+ Induces Formation and Release Of Ceramides And Platelet-activating Factor (Paf) In Vascular Muscle Cells: Potential Rementioning

confidence: 99%

See 3 more Smart Citations

Why there is an Increased Risk of Cardiac Failure, Widening of Pulse Pressure and Hemorrhagic Stroke in Type 2 Diabetics Over Age 60: Roles of Unrecognized Hypomagnesemia and Epigenetics Coupled with Increased Levels of Ceramides, Cytokines, ROS, 4-HNE and Platelet-Activating Factor

Bm¹,

Carella²,

Gebrewold³

et al. 2020

J Clin Case Stu

View full text Add to dashboard Cite

show abstract

Why There is an Increased Number of Deaths from Heroin Mixed with Fentanyl in the USA: Potential Roles of Unrecognized Hypomagnesemia and Elevated Levels of Ceramides and Platelet-Activating Factor Particularly in Brain Stem Area and Potential Relationship to Euphoria and Hallucinations

Altura¹,

Carella²,

Gebrewold³

et al. 2019

Act Scie Pharma

View full text Add to dashboard Cite

Currently, there is a widespread number of deaths, particularly in the USA, from ingestion/imbibing a combination of heroin and fentanyl. Young and old adults are becoming rapidly addicted to this drug combination. Many of these victims believe they are being sold heroin unaware that the latter is often "laced" with fentanyl. Until now, the mechanism(s) for inducing coma followed by death has been thought to be respiratory and cardiac failure. However, new evidence from human and experimental animal studies, reviewed herein, indicates a major underlying cause of euphoria, hallucinations, coma and death is a consequence of cerebrovascular actions in the cerebrum, medulla, and hippocampus which appears to be brought about by rapid, intracellular reduction in free magnesium ions coupled to elevation in cellular and blood levels of ceramides and platelet-activating factor.

show abstract

Extracellular and Intracellular Magnesium Deficiency Found in Pregnant Women with Preeclampsia and Gestational Diabetes Is Associated with Overexpression of Notch Proteins, Cytokines, p53, NF-kB and Proto-Oncogenes: Potential Importance in Growth Retardation, Stillbirths, Fetal Mutations and Increased Cardiovascular Risks and Stroke with Advancing Age in Pregnant Women

Altura

Carella

Shah

et al. 2021

Hearts

View full text Add to dashboard Cite

In 1983, three of us reported in “Science” that umbilical-placental arteries and veins, obtained from normal pregnant women at term delivery, when exposed in vitro to low concentrations of Mg2+ went into vasospasm; the lower the Mg2+, the greater the contractile force developed. These blood vessels also demonstrated amplified contractile force development when challenged with circulating amines and peptides (e.g., norepinephrine, 5-HT, angiotensin II, etc.). We suggested that severe Mg deficiency during pregnancy could in part be responsible for spontaneous abortions, loss of fetuses, stillbirths, and developmental alterations in infants. Using short-term dietary Mg deficient animals, we have noted a great many molecular and biochemical alterations in ventricular, atrial and somatic vascular smooth muscle alterations including DNA methylation and histone changes leading us to speculate that Mg deficiency may represent a genotoxin promoting mutations and causing epigenetic changes. Over the last 35 years, we have new data on severely preeclamptic and gestational diabetic pregnant women that gives credence to our original hypothesis and demonstrates that recently- discovered developmental proteins, originally found 100 years ago in Drosophila fruit flies termed the “Notch pathway”, due to effects on its wings, appears to be important in development of the umbilical-placental blood vessels in pregnant women. Along with the developmental molecule, p53, these Notch proteins clearly alter the behavior of the umbilical-placental vessels. We believe these new findings probably help to explain many of the genetic-toxicity effects seen in women later in life who develop strokes and cardiovascular diseases. Notch alterations could also play an important role in babies born with cardiac defects.

show abstract

Magnesium Deficiency, Sphingolipids, and Telomerase: Relevance to Atherogenesis, Cardiovascular Diseases, and Aging

Cited by 3 publications

References 114 publications

Why there is an Increased Risk of Cardiac Failure, Widening of Pulse Pressure and Hemorrhagic Stroke in Type 2 Diabetics Over Age 60: Roles of Unrecognized Hypomagnesemia and Epigenetics Coupled with Increased Levels of Ceramides, Cytokines, ROS, 4-HNE and Platelet-Activating Factor

Why there is an Increased Risk of Cardiac Failure, Widening of Pulse Pressure and Hemorrhagic Stroke in Type 2 Diabetics Over Age 60: Roles of Unrecognized Hypomagnesemia and Epigenetics Coupled with Increased Levels of Ceramides, Cytokines, ROS, 4-HNE and Platelet-Activating Factor

Why There is an Increased Number of Deaths from Heroin Mixed with Fentanyl in the USA: Potential Roles of Unrecognized Hypomagnesemia and Elevated Levels of Ceramides and Platelet-Activating Factor Particularly in Brain Stem Area and Potential Relationship to Euphoria and Hallucinations

Contact Info

Product

Resources

About