Abstract 14: An Anti-inflammatory Proton Sensing-receptor Contributes To Cardiovascular Protection Of Gut Microbiota-derived Metabolites

• DOI: 10.1161/hyp.78.suppl_1.14
• Publication Date: 2021-08-27T16:36:54Z
• Authors: Liang Xie; Rikeish R Muralit...; Evany Dinakis; Michael E Nakai; Hamdi Jama; Alex Cheng Guan Peh; Caroline Ang; Madeleine Paterson; Ekaterina Salimova; Remy Robert; Charles Mackay; Francine Z Marques
• Keywords: Homeostasis

High fibre (HF) diet protects against hypertension via the production of acidic metabolites, e.g. short-chain fatty acids, by gut microbiota. While these metabolites have a direct role in blood pressure (BP) regulation, their nature may activate proton-sensing receptors, which anti-inflammatory functions. G-protein coupled receptor 65 (GPR65) is activated around pH 6.5 and critical for homeostasis. We hypothesized that GPR65 involved cardiovascular protection dietary fibre. first measured cecal C57BL/6 (WT) mice after 7-day intervention with either HF or low (LF) diets (n=6/group). lowered to level where highly activated, compared LF (6.5±0.1 vs 7.6±0.1, P<0.001). The impact on T cell IFNγ, pro-inflammatory cytokine, vitro was flow cytometry. Acidic inhibited IFNγ CD8+ cells (pH 7.5, Cells lacking had higher at both (P<0.001). To determine if BP regulation fibre, WT knockout ( Gpr65 -/- ) were implanted minipumps containing angiotensin II (Ang II, 0.5mg/kg/day, 28 days, n=8-9/group) fed diet. BP, cardiorenal function immune infiltration measured. 2 weeks (mean arterial ± SEM; 79.8±2.4 95.8±1.6mmHg, P<0.001) 4 Ang infusion (WT 92.3±2.4 99.5±1.3, P=0.062). developed cardiac (P=0.035) renal (P=0.025) hypertrophy, impaired natriuretic (P=0.054) diuretic (P=0.056) mice. This accompanied macrophage (P=0.009) γδ (P=0.014) kidneys. In conclusion, our data suggest pH-sensing contributes inflammatory mechanisms. novel mechanism