The so-called genuine coronary artery spasm leading to myocardial infarction is one of the most insidious diseases that threaten human life, usually overtaking a person in the prime of life and, it would seem, without any apparent reason. In fact, such a reason is always there. A relatively short but powerful contraction of the coronary artery leads to a sharp restriction or complete cessation of coronary blood flow, fatal heart rhythm disturbance and cardiac arrest. The question is what provokes a sudden contraction of the smooth muscles of the vessel and the cessation of blood flow to a significant part of a vital organ. What previous changes in the body and directly in the myocardium can lead to such a development of events - tissue hypoxia, endothelial dysfunction, blockade of glycolysis and outgoing potassium current, increased activity of C and Rho-kinases? Or are there other, as yet little-known, culprits of fatal coronary spasm? Hypoxia is indeed a potent factor that leads to the formation and release of platelet-activating factor (PAF), and PAF acts as a trigger for coronary vasospasm in pig coronary arteries. This compound binds to specific receptors and promotes the activation of phospholipase C and the subsequent formation of inositol 1,4,5-triphosphate and diacylglycerol. The subsequent intracellular calcium release and activation of protein kinase C cause a pronounced contraction of the arteries, which is preserved in a Ca2+-free solution, but is completely eliminated by BN 52021, a potent PAF receptor blocker. Another possible candidate for the role of coronary spasm initiator is our intestine, or more precisely its microbiota. Throughout human life, the intestinal microbiota continuously synthesizes and secretes trimethylamine (TMA) and trimethylamine-N-oxide (TMAO), the chemical structure of which is remarkably similar to that of tetraethylammonium, a known potassium channel blocker. The cumulative inhibitory effect of TMAO ions on the outward potassium current in vascular smooth muscle cells can lead to depolarization of cell membranes and a decrease in their excitability threshold. This creates ideal conditions for the development of smooth muscle hypercontractility and promotes an abnormally high increase in the level of tonic tension in the vascular wall in response to the appearance of a necessary external stimulus, such as a decrease in the oxygenation level. There is evidence that β-hydroxymethylbutyrate helps reduce the formation of trimethylamine in the intestine and helps normalize the qualitative composition of the microbiota, and also prevents the formation of trimethylamine from its precursors contained in food: choline, betaine, carnitine, lecithin, etc. Due to this, the concentration of trimethylamine in the blood and the possibility of its conversion to TMAO are significantly reduced. Blockade of flavin monooxygenase 3 by diindolylmethane, a natural substance from cruciferous vegetables that ensures the conversion of TMA to TMA-O, can significantly enhance the positive effect of hydroxymethylbutyrate, as well as additional administration of leucine, which competes with carnitine. Therefore, a more pronounced effect should be inherent in a combination containing hydroxymethylbutyrate, diindolylmethane and leucine.
Keywords: Coronary Artery Spasm (CAS); Trimethylamine (TMA); Trimethylamine-N-Oxide (TMAO); β-Hydroxymethylbutyrate; Platelet-Activating Factor (PAF)
А Soloviev and V Kozlovsky. “Platelet-Activating Factor (PAF) and Trimethylamine Oxide (TMAO) - Silent Provocateurs of Genuine Coronary Spasm”. ”. EC Pharmacology and Toxicology 12.12 (2024): 01-15.
© 2024 А Soloviev and V Kozlovsky. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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