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The short-chain fatty acid propionate protects from hypertensive cardiovascular damage

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Item Type:Article
Title:The short-chain fatty acid propionate protects from hypertensive cardiovascular damage
Creators Name:Bartolomaeus, H. and Balogh, A. and Yakoub, M. and Homann, S. and Markó, L. and Höges, S. and Tsvetkov, D. and Krannich, A. and Wundersitz, S. and Avery, E.G. and Haase, N. and Kräker, K. and Hering, L. and Maase, M. and Kusche-Vihrog, K. and Grandoch, M. and Fielitz, J. and Kempa, S. and Gollasch, M. and Zhumadilov, Z. and Kozhakhmetov, S. and Kushugulova, A. and Eckardt, K.U. and Dechend, R. and Rump, L.C. and Forslund, S.K. and Müller, D.N. and Stegbauer, J. and Wilck, N.
Abstract:BACKGROUND: Arterial hypertension and its organ sequelae show characteristics of T cell mediated inflammatory diseases. Experimental anti-inflammatory therapies have been shown to ameliorate hypertensive end-organ damage. Recently, the CANTOS study targeting interleukin-1β demonstrated that anti-inflammatory therapy reduces cardiovascular risk. The gut microbiome plays pivotal role in immune homeostasis and cardiovascular health. Short-chain fatty acids (SCFA) are produced from dietary fiber by gut bacteria and affect host immune homeostasis. Here, we investigated effects of the SCFA propionate in two different mouse models of hypertensive cardiovascular damage. METHODS: To investigate the effect of SCFA on hypertensive cardiac damage and atherosclerosis, wild-type NMRI (WT) or ApoE(-/-) deficient mice received propionate (200mM) or control in the drinking water. To induce hypertension, WT mice were infused with Angiotensin (Ang)II (1.44mg/kg/d s.c.) for 14 days. To accelerate the development of atherosclerosis, ApoE(-/-) mice were infused with AngII (0.72mg/kg/d s.c.) for 28 days. Cardiac damage and atherosclerosis were assessed using histology, echocardiography, in vivo electrophysiology, immunofluorescence, and flow cytometry. Blood pressure was measured by radiotelemetry. Regulatory T cell (Treg) depletion using PC61 antibody was used to examine the mode of action of propionate. RESULTS: Propionate significantly attenuated cardiac hypertrophy, fibrosis, vascular dysfunction, and hypertension in both models. Susceptibility to cardiac ventricular arrhythmias was significantly reduced in propionate-treated AngII-infused WT mice. Aortic atherosclerotic lesion area was significantly decreased in propionate-treated ApoE(-/-). Systemic inflammation was mitigated by propionate treatment, quantified as a reduction in splenic effector memory T cell frequencies and splenic T helper 17 cells in both models, and a decrease in local cardiac immune cell infiltration in WT mice. Cardioprotective effects of propionate were abrogated in Treg-depleted AngII-infused mice, suggesting the effect is Treg-dependent. CONCLUSIONS: Our data emphasize an immune-modulatory role of SCFAs and their importance for cardiovascular health. The data suggest that lifestyle modifications leading to augmented SCFA production could be a beneficial non-pharmacological preventive strategy for patients with hypertensive cardiovascular disease.
Keywords:Angiotensin II, APOE, Inflammation, Immunology, Metabolite, Microbiome, Short-Chain Fatty Acids, Regulatory T Cells, Th17 Cells, Bacterial Metabolites, Animals, Mice
Source:Circulation
ISSN:0009-7322
Publisher:American Heart Association (U.S.A.)
Volume:139
Number:11
Page Range:1407-1421
Date:12 March 2019
Additional Information:Copyright © 2018 The Authors
Official Publication:https://doi.org/10.1161/CIRCULATIONAHA.118.036652
PubMed:View item in PubMed

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