Abstract 62: Dietary Fibre Attenuates Hypertension By Reducing Macrophage Infiltration Via Gut Microbiota-Derived Metabolite-Sensing Receptors

Autor: Joanne O'Donnell, Christopher K. Barlow, Charles R. Mackay, Maria Kaparakis-Liaskos, Rikeish R. Muralitharan, Michael E Nakai, Evany Dinakis, Chudan Xu, Madeleine Paterson, Ekaterina Salimova, Natalie J. Bitto, Francine Z Marques, Darren Creek, Hamdi A. Jama, Liang Xie
Rok vydání: 2021
Předmět:
Zdroj: Hypertension. 78
ISSN: 1524-4563
0194-911X
Popis: High dietary fibre is fermented by the gut microbiota, resulting in the release of metabolites called short-chain fatty acids (SCFAs). Both fibre and SCFAs can reduce high blood pressure (BP) and its associated cardio-renal complications. However, the underlying mechanisms remain unclear. SCFAs can be detected by metabolite-sensing receptors GPR41 and GPR43, highly expressed by immune cells such as macrophages. We hypothesised that dietary fibre attenuates hypertension by modulating renal macrophage infiltration via metabolite-sensing receptors GPR41 and GPR43. To test this, we developed a novel GPR41/GPR43 double knockout (DKO) mice and characterised the cardiovascular and immune phenotype in both sham and angiotensin-II (Ang-II, 0.5mg/kg/day) treated DKO and wild-type (WT) mice (n=7-12 per group). WT Ang-II mice fed a high-fibre diet had significantly lower renal galectin-3 (p=0.0004), a macrophage marker, compared to WT Ang-II mice fed a low-fibre diet. Sham DKO mice on standard chow diet had no difference in BP or heart function but had higher kidney/tibia length index (p=0.049) and renal fibrosis levels compared to WT mice (p=0.004). Moreover, untreated DKO mice had higher numbers of renal macrophages compared to WT mice (p=0.002). Ang-II infusion of DKO mice resulted in higher BP (p
Databáze: OpenAIRE