Sodium butyrate suppresses angiotensin II-induced hypertension by inhibition of renal (pro)renin receptor and intrarenal renin–angiotensin system

Wang, Lei; Zhu, Qing; Lu, Aihua; Liu, Xiaofen; Zhang, Linlin; Xu, Chuanming; Liu, Xiyang; Li, Haobo; Yang, Tianxin

doi:10.1097/hjh.0000000000001378

Cited by 143 publications

(107 citation statements)

References 45 publications

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“…Previous studies indicated decreased butyrate-producing bacteria in HTN animal models [18,67]. This study, for the first time, demonstrates that butyrate-producing bacteria and butyrate-producing enzymes significant clustered and separated human REF and HBP cohorts (ANOSIM, P =0.024).…”

Section: Discussionsupporting

confidence: 59%

Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure

et al. 2018

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Recent evidence indicates a link between gut pathology and microbiome with hypertension (HTN) in animal models. However, whether this association exists in humans is unknown. Thus, our objectives in the present study were to test the hypotheses that high blood pressure (BP) patients have distinct gut microbiomes and that gut–epithelial barrier function markers and microbiome composition could predict systolic BP (SBP). Fecal samples, analyzed by shotgun metagenomics, displayed taxonomic and functional changes, including altered butyrate production between patients with high BP and reference subjects. Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability. Zonulin, a gut epithelial tight junction protein regulator, was markedly elevated, further supporting gut barrier dysfunction in high BP. Zonulin strongly correlated with SBP (R2 = 0.5301, P<0.0001). Two models predicting SBP were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of SBP from zonulin in plasma (R2 = 0.4608, P<0.0001). The mouse model of HTN, chronic angiotensin II (Ang II) infusion, was used to confirm the effects of butyrate and gut barrier function on the cardiovascular system and BP. These results support our conclusion that intestinal barrier dysfunction and microbiome function are linked to HTN in humans. They suggest that manipulation of gut microbiome and its barrier functions could be the new therapeutic and diagnostic avenues for HTN.

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Section: Discussionsupporting

confidence: 59%

Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure

et al. 2018

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“…NaBu is generated from butyrate, an important bioactive metabolite produced by gut microbiota. We have previously reported that intrarenal administration of NaBu exerts mild anti‐hypertrophic effect on the hearts in Ang II‐induced hypertensive rats . Consistent with our results, Patel BM and colleagues have recently reported that NaBu has beneficial effect on cardiac hypertrophy in partial abdominal aortic constriction (PAAC) rat model .…”

Section: Discussionsupporting

confidence: 90%

“…NaBu is also reported to work as an inhibitor of histone deacetylases (HDACs) to modulate gene expression and control cardiac hypertrophy in experimental rat model . Our most recent study finds that intrarenal administration of NaBu suppresses Ang II‐induced hypertension by inhibition of renal (pro)renin receptor and exerts anti‐hypertrophic effects on the heart . However, it still remains unknown whether and how systemic administration of NaBu protects against the cardiac hypertrophy induced by Ang II.…”

Section: Introductionmentioning

confidence: 99%

Sodium butyrate attenuates angiotensin II‐induced cardiac hypertrophy by inhibiting COX2/PGE2 pathway via a HDAC5/HDAC6‐dependent mechanism

Zhang

Deng

et al. 2019

J Cellular Molecular Medi

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Sodium butyrate (NaBu) is reported to play important roles in a number of chronic diseases. The present work is aimed to investigate the effect of NaBu on angiotensin II (Ang II)‐induced cardiac hypertrophy and the underlying mechanism in in vivo and in vitro models. Sprague Dawley rats were infused with vehicle or Ang II (200 ng/kg/min) and orally administrated with or without NaBu (1 g/kg/d) for two weeks. Cardiac hypertrophy parameters and COX2/PGE2 pathway were analysed by real‐time PCR, ELISA, immunostaining and Western blot. The cardiomyocytes H9C2 cells were used as in vitro model to investigate the role of NaBu (2 mmol/L) in inhibition of Ang II‐induced cardiac hypertrophy. NaBu significantly attenuated Ang II‐induced increase in the mean arterial pressure. Ang II treatment remarkably increased cardiac hypertrophy as indicated by increased ratio of heart weight/body weight and enlarged cardiomyocyte size, extensive fibrosis and inflammation, as well as enhanced expression of hypertrophic markers, whereas hearts from NaBu‐treated rats exhibited a significant reduction in these hypertrophic responses. Mechanistically, NaBu inhibited the expression of COX2/PGE2 along with production of ANP and phosphorylated ERK (pERK) stimulated by Ang II in in vivo and in vitro, which was accompanied by the suppression of HDAC5 and HDAC6 activities. Additionally, knocking down the expression of HDAC5 and HDAC6 via gene‐editing strategy dramatically blocked Ang II‐induced hypertrophic responses through COX2/PGE2 pathway. These results provide solid evidence that NaBu attenuates Ang II‐induced cardiac hypertrophy by inhibiting the activation of COX2/PGE2 pathway in a HDAC5/HDAC6‐dependent manner.

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“…Furthermore, fibre‐rich diets or magnesium acetate and oral minocycline supplementation could restore gut microbiota homeostasis, reduce the F/B ratio and attenuate BP levels (Yang, et al , ; Marques, et al , ). In addition, treatment with propionate or butyrate could protect the host from cardiac damage in experimental hypertension models (Wang, et al , ; Bartolomaeus, et al , ). In summary, solid data clearly demonstrate the involvement and therapeutic potential of SCFAs in hypertension.…”

Section: Interactions Between the Gut Microbiota And Cvdmentioning

confidence: 99%

The gut microbiota and its interactions with cardiovascular disease

Wang

Feng

et al. 2020

Microbial Biotechnology

115

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Summary The intestine is colonized by a considerable community of microorganisms that cohabits within the host and plays a critical role in maintaining host homeostasis. Recently, accumulating evidence has revealed that the gut microbial ecology plays a pivotal role in the occurrence and development of cardiovascular disease (CVD). Moreover, the effects of imbalances in microbe–host interactions on homeostasis can lead to the progression of CVD. Alterations in the composition of gut flora and disruptions in gut microbial metabolism are implicated in the pathogenesis of CVD. Furthermore, the gut microbiota functions like an endocrine organ that produces bioactive metabolites, including trimethylamine/trimethylamine N‐oxide, short‐chain fatty acids and bile acids, which are also involved in host health and disease via numerous pathways. Thus, the gut microbiota and its metabolic pathways have attracted growing attention as a therapeutic target for CVD treatment. The fundamental purpose of this review was to summarize recent studies that have illustrated the complex interactions between the gut microbiota, their metabolites and the development of common CVD, as well as the effects of gut dysbiosis on CVD risk factors. Moreover, we systematically discuss the normal physiology of gut microbiota and potential therapeutic strategies targeting gut microbiota to prevent and treat CVD.

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Sodium butyrate suppresses angiotensin II-induced hypertension by inhibition of renal (pro)renin receptor and intrarenal renin–angiotensin system

Abstract: These results demonstrate that NaBu exerts an antihypertensive action, likely by suppressing the PRR-mediated intrarenal renin-angiotensin system.

Cited by 143 publications

References 45 publications

Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure

Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure

Sodium butyrate attenuates angiotensin II‐induced cardiac hypertrophy by inhibiting COX2/PGE2 pathway via a HDAC5/HDAC6‐dependent mechanism

The gut microbiota and its interactions with cardiovascular disease

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