The role of dietary magnesium deficiency in inflammatory hypertension.
The role of dietary magnesium deficiency in inflammatory hypertension.
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DOI：
10.3389/fphys.2023.1167904
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发表时间：
2023
影响因子：
4
通讯作者：
中科院分区：
文献类型：
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近30%的成年人摄入的镁（Mg 2+）低于估计的平均每日需求量，而常用的药物，如利尿剂，会促进Mg 2+缺乏。较高的血清Mg 2+水平、膳食Mg 2+摄入量增加和Mg 2+补充均与血压降低相关，表明Mg 2+缺乏有助于高血压的发病机制。抗原呈递细胞，如单核细胞和树突状细胞，是众所周知的参与高血压的发病机制。在这些细胞中，血压升高所必需的过程包括NLRP 3炎性体的激活、IL-1β的产生和脂肪酸如花生四烯酸的氧化修饰，形成异evuglandins（IsoLG）。我们假设，饮食Mg 2+耗竭引起的血压升高导致抗原呈递细胞中NLRP 3、IL-1β和IsoLG的产生增加。我们发现，与喂食0.08%Mg2+饮食的小鼠相比，Mg 2+耗尽饮食（0.01%Mg2+饮食）增加了小鼠的血压。通过定量磁共振测量，Mg 2+耗尽小鼠的总体液没有增加。血浆IL-1β浓度升高（0.13 ± 0.02 pg/mL vs. 0.04 ± 0.02 pg/mL）。使用流式细胞术，我们观察到脾、肾和主动脉的抗原呈递细胞中NLRP 3和IL-1β表达增加。我们还观察到这些器官的抗原呈递细胞中IsoLG的产生增加。CD 11 c+树突状细胞的原代培养证实，低细胞外Mg 2+对这些细胞产生直接影响，刺激IL-1β和IL-18的产生。目前的研究结果表明，NLRP 3炎性小体激活和IsoLG-加合物的形成刺激时，饮食镁2+耗尽。干预措施和增加饮食中镁的摄入量可能有助于降低高血压和心血管疾病的患病率。
Nearly 30% of adults consume less than the estimated average daily requirement of magnesium (Mg2+), and commonly used medications, such as diuretics, promote Mg2+ deficiency. Higher serum Mg2+ levels, increased dietary Mg2+ in-take, and Mg2+ supplementation are each associated with lower blood pressure, suggesting that Mg2+-deficiency contributes to the pathogenesis of hypertension. Antigen-presenting cells, such as monocytes and dendritic cells, are well-known to be involved in the pathogenesis of hypertension. In these cells, processes implicated as necessary for increased blood pressure include activation of the NLRP3 inflammasome, IL-1β production, and oxidative modification of fatty acids such as arachidonic acid, forming isolevuglandins (IsoLGs). We hypothesized that increased blood pressure in response to dietary Mg2+-depletion leads to increased NLRP3, IL-1β, and IsoLG production in antigen presenting cells. We found that a Mg2+-depleted diet (0.01% Mg2+ diet) increased blood pressure in mice compared to mice fed a 0.08% Mg2+ diet. Mg2+-depleted mice did not exhibit an increase in total body fluid, as measured by quantitative magnetic resonance. Plasma IL-1β concentrations were increased (0.13 ± 0.02 pg/mL vs. 0.04 ± 0.02 pg/mL). Using flow cytometry, we observed increased NLRP3 and IL-1β expression in antigen-presenting cells from spleen, kidney, and aorta. We also observed increased IsoLG production in antigen-presenting cells from these organs. Primary culture of CD11c+ dendritic cells confirmed that low extracellular Mg2+ exerts a direct effect on these cells, stimulating IL-1β and IL-18 production. The present findings show that NLRP3 inflammasome activation and IsoLG-adduct formation are stimulated when dietary Mg2+ is depleted. Interventions and increased dietary Mg2+ consumption may prove beneficial in decreasing the prevalence of hypertension and cardiovascular disease.
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