The Crosstalk between Calcium Ions and Aldosterone Contributes to Inflammation, Apoptosis, and Calcification of VSMC via the AIF-1/NF-κB Pathway in Uremia

Abstract

Vascular calcification is a major complication of maintenance hemodialysis patients. Studies have confirmed that calcification mainly occurs in the vascular smooth muscle cells (VSMC) of the vascular media. However, the exact pathogenesis of VSMC calcification is still unknown. This study shows that the crosstalk between calcium and aldosterone via the allograft inflammatory factor 1 (AIF-1) pathway contributes to calcium homeostasis and VSMC calcification, which is a novel mechanism of vascular calcification in uremia. In vivo results showed that the level of aldosterone and inflammatory factors increased in calcified arteries, whereas no significant changes were observed in peripheral blood. However, the expression of inflammatory factors markedly increased in the peripheral blood of uremic rats without aortic calcification and gradually returned to normal levels with aggravation of aortic calcification. In vitro results showed that there was an interaction between calcium ions and aldosterone in macrophages or VSMC. Calcium induced aldosterone synthesis, and in turn, aldosterone also triggered intracellular calcium content upregulation in macrophages or VSMC. Furthermore, activated macrophages induced inflammation, apoptosis, and calcification of VSMC. Activated VSMC also imparted a similar effect on untreated VSMC. Finally, AIF-1 enhanced aldosterone- or calcium-induced VSMC calcification, and NF-κB inhibitors inhibited the effect of AIF-1 on VSMC. These in vivo and in vitro results suggest that the crosstalk between calcium ions and aldosterone plays an important role in VSMC calcification in uremia via the AIF-1/NF-κB pathway. Local calcified VSMC induced the same pathological process in surrounding VSMC, thereby contributing to calcium homeostasis and accelerating vascular calcification.

Magnesium supplementation reduces inflammation in rats with induced chronic kidney disease

“…Previous studies aimed at addressing mechanistic insights on the protective effect of Mg on vascular cells gave relevance to the properties of Mg as a calcium antagonist, 1 so that calcium action is susceptible of being modified by the Mg supplement. A rise in the intracellular calcium can activate transduction pathways leading to an increase in oxidative stress, the activation of the NF‐κB signalling and the production of pro‐inflammatory cytokines 49,50 . Thus, as a physiological inhibitor of calcium channels, Mg might prevent calcium flux and therefore the inflammatory response.…”

Vascular Calcification in Chronic Kidney Disease: An Update and Perspective

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SR-A-Targeted Nanoplatform for Sequential Photothermal/Photodynamic Ablation of Activated Macrophages to Alleviate Atherosclerosis

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