Abstract 016: Magnesium Deficient Diet-induced Hypertension And Renal DC-specific NLRP3 Inflammasome Activation

Abstract

Background: Analysis from a 2013-2016 dietary survey by the National Health and Nutrition Examination Survey Several found that less than 50% of Americans consume sufficient magnesium. Multiple studies have identified a link between dietary magnesium and inflammation associated with multiple pathologies including hypertension, chronic kidney disease, and cardiovascular disease. Additionally, magnesium sulfate inhibits NLRP3 inflammasome activation in human macrophages. We have previously shown that activation of the NLRP3 inflammasome is a key component of salt-sensitive hypertension. In this study, we hypothesize that a magnesium-deficient diet could promote NLRP3 inflammasome activation in myeloid cells and systemic hypertension. Materials and Methods: In vivo studies were performed on mice with an SV/129 background given either a normal-magnesium (Norm-Mg 2+ ) diet (0.08%, as magnesium oxide) or low-magnesium (Low-Mg 2+ ) diet (0.01%) for 5 weeks. Systolic blood pressure (SBP) was monitored on a weekly basis by tail-cuff. Results: Mice fed a Low-Mg 2+ diet had a significant increase in SBP compared to the Norm-Mg 2+ diet fed mice (105.8 ± 11.3 to 130.4 ± 7.4 mmHg vs 106.5 ± 9.4 to 121.8 ± 6.5 mmHg, [n=7, p=0.0071, 2 way ANOVA]). Using flow cytometry, we observed an increase in NLRP3 (34.1 ± 2.5 vs 7.4 ± 0.6 % of DCs, [n=5-7, p=0.0025, Mann-Whitney test]) and IL-1β (41.9 ± 6.6 vs 15.86 ± 6.6 % of DCs, [n=5-7, p=0.048, Mann-Whitney test]) expression in renal dendritic cells (DCs) of Low-Mg 2+ mice compared to Norm-Mg 2+ mice. There was a similar increase in IsoLG-adduct formation in renal DCs (8.5 ± 2.0 vs 0.6 ± 0.05 % of DCs, [n=5-7, p=0.0025, Mann-Whitney test). Interestingly, we found no difference in NLRP3 (24.92 ± 5.3 vs 31.54 ± 3.1 % of monocytes, [n=5-7, p=0.1376, Mann-Whitney test]), IL-1β (9.5 ± 4.3 vs 4.6 ± 0.4 % of monocytes, [n=5-7, p=0.7551, Mann-Whitney test]), or IsoLG-adduct formation (29.42 ± 3.6 vs 31.9 ± 3.6 % of monocytes, [n=5-7, p=<0.999, Mann-Whitney test]) in renal monocytes. Conclusions: Our findings suggest a magnesium-deficient diet induces a hypertensive response and activates the NLRP3 inflammasome in renal DCs but not monocytes.