Short-Chain Fatty Acid Propionate Protects From Hypertensive Cardiovascular Damage

Bartolomaeus, Hendrik; Balogh, András; Yakoub, Mina; Homann, Susanne; Markó, Lajos; Höges, Sascha; Tsvetkov, D; Krannich, Alexander; Wundersitz, Sebastian; Avery, Ellen G.; Haase, Nadine; Kräker, Kristin; Hering, Lydia; Maase, Martina; Kusche-Vihrog, Kristina; Grandoch, Maria; Fielitz, Jens; Kempa, Stefan; Gollasch, Maik; Zhumadilov, Zhaxybay; Kozhakhmetov, Samat; Kushugulova, Аlmagul; Eckardt, Kai Uwe; Dechend, Ralf; Rump, Lars Christian; Forslund, Kristoffer; Müller, Dominik N.; Stegbauer, Johannes; Wilck, Nicola

doi:10.1161/circulationaha.118.036652

Cited by 509 publications

(415 citation statements)

References 50 publications

(71 reference statements)

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“…Chronic inflammation can lead to injury in the cardiovascular system, whereas anti-inflammatory Treg cells could secrete anti-inflammatory IL-10 to ameliorate cardiovascular syndrome. Supplementation with propionate promotes the anti-inflammatory response of Treg cells to reduce local infiltration of immune cells, thereby reducing cardiac hypertrophy and fibrosis, susceptibility to cardiac arrhythmias, and atherosclerotic lesion burden and exhibits antihypertensive effects in angiotensin II (Ang II)-induced hypertension or atherosclerosis NMRI mice model [93]. Also, propionate alleviates cardiomyocyte contractile dysfunction via regulating the expression of protein phosphatases, eNOS, and phosphorylated PTEN and GSK3β in AKT2-knockout mice [94].…”

Section: Propionate and Propionylationmentioning

confidence: 99%

Short-chain fatty acid, acylation and cardiovascular diseases

2020

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Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide. Metabolic dysfunction is a fundamental core mechanism underlying CVDs. Previous studies generally focused on the roles of long-chain fatty acids (LCFAs) in CVDs. However, a growing body of study has implied that short-chain fatty acids (SCFAs: namely propionate, malonate, butyrate, 2-hydroxyisobutyrate (2-HIBA), β-hydroxybutyrate, crotonate, succinate, and glutarate) and their cognate acylations (propionylation, malonylation, butyrylation, 2-hydroxyisobutyrylation, β-hydroxybutyrylation, crotonylation, succinylation, and glutarylation) participate in CVDs. Here, we attempt to provide an overview landscape of the metabolic pattern of SCFAs in CVDs. Especially, we would focus on the SCFAs and newly identified acylations and their roles in CVDs, including atherosclerosis, hypertension, and heart failure. Clinical Science (2020) 134 657-676 https://doi.org/10.1042/CS20200128 cofactors in certain protein acylations, such as propionylation [14], malonylation [15], butyrylation [14], 2-hydroxyisobutyrylation [16], β-hydroxybutyrylation [17], crotonylation [18], succinylation [19], and glutarylation [20]. These discoveries give us a deeper understanding of PTM. Among PTMs, protein acetylation is the earliest discovered and most studied. Similar to protein acetylation, various studies have shown that these newly discovered PTMs are also involved in physiological and pathophysiological processes, including cardiovascular homeostasis.Here in this review, we will summarize SCFAs, protein acylations, and their emerging roles in CVDs, including atherosclerosis, hypertension, and heart failure. The metabolic pattern and FAs in CVDsThe heart is an 'omnivore' , using FAs, glucose, lactate, ketone bodies, and amino acids as metabolic substrates [5,6]. The substrates utilized by the embryonic heart are significantly different from those used by the adult heart. The embryonic heart depends primarily on glycolysis as well as lactate oxidation to produce energy [21]. The newborn and adult heart shift toward the remarkable utilization of FAs to meet cardiac energy demand [5,9]. In failing hearts, a decrease in FA oxidation and an increase in glycolysis are critically involved in cardiac dysfunction [22]. As thus, the metabolic pattern is essential for maintaining cardiac and vascular functions.Diabetes, hypertension, and obesity contribute to heart failure syndrome. Accumulating evidence suggests that hypertension, ischemic hearts, and heart failure induce a shift in substrate toward the remarkable utilization of glucose to generate energy. Despite this shift, the FA oxidation remains to make much energy for the diseased heart [23]. Since FAs are the predominant substrates for cardiomyocytes, alterations in FA metabolism have been implicated as causal in cardiac diseases. FAs within cells and in the circulation are critically involved in cardiometabolic diseases. CVDs are closely associated with lifestyle and metabolic status, which affect circul...

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Section: Propionate and Propionylationmentioning

confidence: 99%

Short-chain fatty acid, acylation and cardiovascular diseases

2020

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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%

“…In a cohort study, decreased plasma primary BA levels and increased specific secondary BA levels have been observed in patients with chronic HF (Mayerhofer, et al , ). The SCFA propionate significantly attenuated cardiac hypertrophy, fibrosis and vascular dysfunction, mainly via regulatory T cells (Bartolomaeus, et al , ). Besides the gut metabolites mentioned above, phenyl‐acetyl‐glutamine (PAG) is a strong and independent risk factor for CVD and mortality (Poesen, et al , ), and p‐cresyl sulfate (PCS) might function as a predictor of cardiovascular events and all‐cause mortality (Lin, et al , ) (Table ).…”

Section: Interactions Between the Gut Microbiota And Cvdmentioning

confidence: 99%

“…SCFAs, such as butyrate, have received increasing interest in relation to hypertension, and their main effects are modulation of the microbial composition and inflammation reduction (Wang, et al , ; Kim, et al , ). Propionate also exhibits hypotensive effects, possibly via expansion of the splenic Treg cell population (Bartolomaeus, et al , ).…”

Section: The Link Between the Gut Microbiota And Cvd‐related Risk Facmentioning

confidence: 99%

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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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“…Recently, propionate has also been shown to significantly attenuate cardiac hypertrophy, fibrosis, vascular dysfunction, and hypertension in two different mouse models of hypertensive cardiovascular damage [97], even if its precise role in HF remains largely undetermined. Gut microbiota is also involved in the secondary conversion of BA synthesized by the liver, modulating gut microbial composition, activating innate immune response genes in the small intestine [98], affecting in turn weight management and obesity, insulin secretion and sensitivity, hepatic lipid metabolism and hypertension [98].…”

Section: Role Of Gut Microbiota In Hfmentioning

confidence: 99%

Novel Basic Science Insights to Improve the Management of Heart Failure: Review of the Working Group on Cellular and Molecular Biology of the Heart of the Italian Society of Cardiology

Ameri

Schiattarella

Crotti

et al. 2020

IJMS

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Despite important advances in diagnosis and treatment, heart failure (HF) remains a syndrome with substantial morbidity and dismal prognosis. Although implementation and optimization of existing technologies and drugs may lead to better management of HF, new or alternative strategies are desirable. In this regard, basic science is expected to give fundamental inputs, by expanding the knowledge of the pathways underlying HF development and progression, identifying approaches that may improve HF detection and prognostic stratification, and finding Int.

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Short-Chain Fatty Acid Propionate Protects From Hypertensive Cardiovascular Damage

Abstract: Supplemental Digital Content is available in the text.

Cited by 509 publications

References 50 publications

Short-chain fatty acid, acylation and cardiovascular diseases

Short-chain fatty acid, acylation and cardiovascular diseases

The gut microbiota and its interactions with cardiovascular disease

Novel Basic Science Insights to Improve the Management of Heart Failure: Review of the Working Group on Cellular and Molecular Biology of the Heart of the Italian Society of Cardiology

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