Acta Physiologica最新文献

IgE acts primarily via the high affinity IgE receptor (FcεRI) and is central to immediate hypersensitivity reactions (anaphylaxis). However, IgE is also important in the development of chronic hypersensitivity reactions (allergy). In the cardiovascular system, numerous clinical studies have investigated serum IgE levels, mainly in the context of myocardial infarction, and have established a clear association between IgE and ischemic cardiac events. While animal studies demonstrate that IgE can cause atherosclerotic plaque formation, this is complicated by clinical reports that IgE is associated with non-fatal ischemic events and not with fatal events, raising the possibility that IgE could be protective in this setting. In terms of non-ischemic cardiac disease, little information is available clinically for IgE; however, animal models also indicate that IgE promotes adverse effects in this setting as well. This review article will present the clinical studies that have established a relationship between serum IgE levels and cardiac disease, particularly myocardial infarction. This review article will also discuss animal studies that provide mechanistic understanding of how IgE can exert chronic effects in the heart. This article also attempts to address the question of whether IgE is causative of cardiac disease or is a response to cardiac disease.

Ca²⁺ and Mg²⁺ are essential nutrients, and deficiency can cause serious health problems. Thus, lack of Ca²⁺ and Mg²⁺ can lead to osteoporosis, with incidence rising both in absolute and age-specific terms, while Mg²⁺ deficiency is associated with type II diabetes. Prevention via vitamin D or estrogen is controversial, and the bioavailability of Ca²⁺ and Mg²⁺ from supplements is significantly lower than that from milk products. Problems are likely to increase as populations age and the number of people on vegan diets surges. Developing new therapeutic strategies requires a better understanding of the molecular mechanisms involved in absorption by intestinal epithelia. The vitamin-D dependent, active pathway for the uptake of Ca²⁺ from the upper small intestine involving TRPV6 is highly efficient but only accounts for about 20% of total uptake. Instead, most Ca²⁺ uptake is thought to occur via passive paracellular diffusion across the ileum, although sufficiently high luminal concentrations are difficult to achieve.. Interestingly, colon and caecum also have a considerable capacity for the active absorption of Ca²⁺ and Mg²⁺, the molecular mechanisms of which are unclear. Intriguingly, stimulating fermentation by prebiotics enhances colonic absorption, which can rise from ~10% to ~30% of the total. Notably, fermentation releases protons, which inhibits channels highly selective for Ca²⁺ and Mg²⁺ (TRPV6 and TRPM6/TRPM7). Conversely, the non-selective cation channel TRPV3 is stimulated by both intracellular acidification and by numerous herbal compounds. Spicy, fiber-rich food, as traditionally consumed in many cultures, might enhance the uptake of Ca²⁺ and Mg²⁺ via this pathway.

Preserving the balance of metabolic processes in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), is crucial for optimal vascular function and integrity. ECs are metabolically active and depend on aerobic glycolysis to efficiently produce energy for their essential functions, which include regulating vascular tone. Impaired EC metabolism is linked to endothelial damage, increased permeability and inflammation. Metabolic alterations in VSMCs also contribute to vascular dysfunction in atherosclerosis and hypertension. Magnesium (Mg²⁺) is the second most abundant intracellular divalent cation and influences molecular processes that regulate vascular function, including vasodilation, vasoconstriction, and release of vasoactive substances. Mg²⁺ is critically involved in maintaining cellular homeostasis and metabolism since it is an essential cofactor for ATP, nucleic acids and hundreds of enzymes involved in metabolic processes. Low Mg²⁺ levels have been linked to endothelial dysfunction, increased vascular tone, vascular inflammation and arterial remodeling. Growing evidence indicates an important role for the transient receptor potential melastatin-subfamily member 7 (TRPM7) cation channel in the regulation of Mg²⁺ homeostasis in EC and VSMCs. In the vasculature, TRPM7 deficiency leads to impaired endothelial function, increased vascular contraction, phenotypic switching of VSMCs, inflammation and fibrosis, processes that characterize the vascular phenotype in hypertension. Here we provide a comprehensive overview on TRPM7/Mg²⁺ in the regulation of vascular function and how it influences EC and VSMC metabolism such as glucose and energy homeostasis, redox regulation, phosphoinositide signaling, and mineral metabolism. The putative role of TRPM7/Mg²⁺ and altered cellular metabolism in vascular dysfunction and hypertension is also discussed.