Abstract 026: Gut Bacteria Metabolite Attenuates Ang II-induced Cardiac Damage
Increasing evidence suggests that the gut microbiota critically influence host health and immune homeostasis. Microbiome-host communication occurs via gut bacterial metabolites which are resorbed by the host and target various organs. Short-chain fatty acids (SCFA) are produced from bacterial fermentation, are highly abundant in the gut but can also be detected in the blood. Recently, the SCFA propionate has been shown to regulate T cell differentiation into effector and regulatory T cells in peripheral tissues. Since activation of the immune system is known to substantially contribute to hypertensive target organ damage and anti-inflammatory strategies have been shown to be beneficial in animal models, we hypothesized that treatment with propionate would be beneficial in angiotensin (AngII)-induced target organ damage. Male NMRI mice received AngII infusions for two weeks and propionate (P) or vehicle (C) in drinking water. To deplete endogenous SCFA production mice were fed a low-fibre diet. Body weight was similar among all groups. Propionate treatment significantly reduced albuminuria (C 1143 ± 193; P 302 ± 69 μg/d). Propionate significantly reduced cardiac hypertrophy as measured by heart-to-tibia ratio (C 10.1 ± 0.4; P 8.9 ± 0.4 mg/mm) and was confirmed by echocardiography. Propionate treatment significantly reduced interstitial (C 16.5 ± 0.8%; P 6.6 ± 0.2%) and perivascular cardiac fibrosis (C 1.5 ± 0.06; P 1.1 ± 0.03 μm/μm) as measured by fibronectin and collagen I immunofluorescence, respectively. In vivo cardiac electrophysiology studies showed a significantly reduced susceptibility to ventricular arrhythmias in propionate-treated mice (C 71 ± 14%; P 24 ± 16%), indicating the functional relevance of the improved cardiac morphology. Propionate reduced the expression of IL-17 in CD4+ T cells in spleen and lymph nodes as measured by flow cytometry. Our data indicate that propionate attenuates AngII-induced cardiac remodeling and reduces susceptibility to arrhythmias. The gut microbiome is a promising target for treatment of hypertensive heart disease.
Author Disclosures: N. Wilck: None. H. Bartolomaeus: None. A. Balogh: None. L. Marko: None. R. Dechend: None. D. Müller: None.
- © 2015 by American Heart Association, Inc.