Abstract 131: Microbiota-Derived Metabolite Propionate Protects From Hypertensive Cardiovascular Damage

Nicola Wilck, Hendrik Bartolomaeus, András Balogh, Mina Yakoub, Susanne Homann, Lajos Markó, Sascha Höges, Dmitry Tsvetkov, Sebastian Wundersitz, Nadine Haase

13 more authors

Lydia Hering, Martina Maase, Kristina Kusche‐Vihrog, Maria Grandoch, Jens Fielitz, Stefan Kempa, Sofia Kirke Forslund, Almagul R. Kushugulova, Ralf Dechend, Kai‐Uwe Eckardt, Lars Christian Rump, Dominik Müller, Johannes Stegbauer

2018

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DOI 10.1161/hyp.72.suppl_1.131
Data confidence 70 medium
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Abstract

Objective: Inflammation drives cardiovascular disease, anti-inflammatory approaches may be beneficial. Short-chain fatty acids (SCFA) are bacterial metabolites with anti-inflammatory properties affecting host immune homeostasis including regulatory T cells (Treg). We investigated effects of the SCFA propionate (administered in drinking water, NaCl as control) in two mouse models, namely hypertensive heart disease (wild-type NMRI (WT), angiotensin (Ang)II infusion 1.44 mg/kg/d s.c. for 14 days) and atherosclerosis (Apolipoprotein E knockout (ApoE), AngII infusion 0.72 mg/kg/d s.c. for 28 days), respectively. Results: Propionate attenuated cardiac hypertrophy and fibrosis in both models significantly. Susceptibility to cardiac ventricular arrhythmias was significantly reduced in propionate-treated WT mice. Aortic atherosclerotic lesion area was significantly reduced in propionate-treated ApoE (27.6±8 vs. 7.9±2.4%). Treatment reduced splenic effector memory (CD4+ CD44+ CD62L-) T cell frequencies (WT: 30.5±4.6 vs. 19.1±1.6; ApoE: 41.1±3.1 vs. 32.7±1.4%) and splenic Th17 cells (WT: 1.0±0.2 vs. 0.6±0.1; ApoE: 1.3±0.1 vs. 0.9±0.1%) in both models, indicating beneficial effects on systemic inflammation. Similarly, propionate reduced cardiac immune cell infiltration (CD4+, CD8+, F4/80+) in WT mice. Propionate improved vascular dysfunction and moderately reduced blood pressure in both models. Organ-protective actions of propionate (cardiac inflammation and fibrosis) were abrogated in Treg-depleted (antiCD25-treated) AngII-infused WT mice, suggesting a central role for Treg. To verify our findings in a human cohort, we re-analyzed clinical and metagenomic data from a recent randomized controlled trial investigating the effect of a 90-day synbiotic intervention in 84 subjects with metabolic syndrome including healthy controls. Interestingly, in synbiotic-treated subjects an increased capacity for SFCA production was significantly correlated to blood pressure reduction. Conclusion: Data underscore the importance of SCFA for cardiovascular health and suggest that lifestyle modifications leading to augmented SCFA production could be a beneficial non-pharmacological add-on strategy for cardiovascular disease.