3-(3-Hydroxyphenyl)propionic acid, a microbial metabolite of quercetin, inhibits monocyte binding to endothelial cells via modulating E-selectin expression

Human endothelial cells (HUVEC) can metabolize the isoflavones genistein and daidzein into phase II conjugates, but not the majorin vivomicrobial metabolite of daidzein, equol.

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Microbial metabolite indole-3-propionic acid supplementation does not protect mice from the cardiometabolic consequences of a Western diet

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00375.2019 ◽

2020 ◽

Vol 319 (1) ◽

pp. G51-G62

Author(s):

Dustin M. Lee ◽

Kayl E. Ecton ◽

S. Raj J. Trikha ◽

Scott D. Wrigley ◽

Keely N. Thomas ◽

...

Keyword(s):

Gut Microbiota ◽

Propionic Acid ◽

Western Diet ◽

Tryptophan Metabolism ◽

Metabolic Effects ◽

Microbial Metabolites ◽

Microbial Metabolite ◽

Acid Supplementation ◽

Host Health ◽

Circulating Levels

The gut microbiota has been shown to mediate host health. Emerging data implicate gut microbial metabolites of tryptophan metabolism as potential important mediators. We examined the effects of indole-3-propionic acid in Western diet-fed mice and found no beneficial cardiometabolic effects. Our data do not support the supposition that indole-3-propionic acid (IPA) mediates beneficial metabolic effects downstream of the gut microbiota and may be potentially deleterious in higher circulating levels.

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Gut-Derived Metabolite Indole-3-Propionic Acid Modulates Mitochondrial Function in Cardiomyocytes and Alters Cardiac Function

Frontiers in Medicine ◽

10.3389/fmed.2021.648259 ◽

2021 ◽

Vol 8 ◽

Author(s):

Maren Gesper ◽

Alena B. H. Nonnast ◽

Nina Kumowski ◽

Robert Stoehr ◽

Katharina Schuett ◽

...

Keyword(s):

Heart Failure ◽

Endothelial Cells ◽

Fatty Acid ◽

Cardiac Function ◽

Mitochondrial Dysfunction ◽

Propionic Acid ◽

Mitochondrial Function ◽

Mitochondrial Respiration ◽

Acid Oxidation ◽

Microbial Metabolites

Background: The gut microbiome has been linked to the onset of cardiometabolic diseases, in part facilitated through gut microbiota-dependent metabolites such as trimethylamine-N-oxide. However, molecular pathways associated to heart failure mediated by microbial metabolites remain largely elusive. Mitochondria play a pivotal role in cellular energy metabolism and mitochondrial dysfunction has been associated to heart failure pathogenesis. Aim of the current study was to evaluate the impact of gut-derived metabolites on mitochondrial function in cardiomyocytes via an in vitro screening approach.Methods: Based on a systematic Medline research, 25 microbial metabolites were identified and screened for their metabolic impact with a focus on mitochondrial respiration in HL-1 cardiomyocytes. Oxygen consumption rate in response to different modulators of the respiratory chain were measured by a live-cell metabolic assay platform. For one of the identified metabolites, indole-3-propionic acid, studies on specific mitochondrial complexes, cytochrome c, fatty acid oxidation, mitochondrial membrane potential, and reactive oxygen species production were performed. Mitochondrial function in response to this metabolite was further tested in human hepatic and endothelial cells. Additionally, the effect of indole-3-propionic acid on cardiac function was studied in isolated perfused hearts of C57BL/6J mice.Results: Among the metabolites examined, microbial tryptophan derivative indole-3-propionic acid could be identified as a modulator of mitochondrial function in cardiomyocytes. While acute treatment induced enhancement of maximal mitochondrial respiration (+21.5 ± 7.8%, p < 0.05), chronic exposure led to mitochondrial dysfunction (−18.9 ± 9.1%; p < 0.001) in cardiomyocytes. The latter effect of indole-3-propionic acids could also be observed in human hepatic and endothelial cells. In isolated perfused mouse hearts, indole-3-propionic acid was dose-dependently able to improve cardiac contractility from +26.8 ± 11.6% (p < 0.05) at 1 μM up to +93.6 ± 14.4% (p < 0.001) at 100 μM. Our mechanistic studies on indole-3-propionic acids suggest potential involvement of fatty acid oxidation in HL-1 cardiomyocytes.Conclusion: Our data indicate a direct impact of microbial metabolites on cardiac physiology. Gut-derived metabolite indole-3-propionic acid was identified as mitochondrial modulator in cardiomyocytes and altered cardiac function in an ex vivo mouse model.

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3-(4-Hydroxyphenyl)propionic acid, a major microbial metabolite of procyanidin A2, shows similar suppression of macrophage foam cell formation as its parent molecule

RSC Advances ◽

10.1039/c7ra13729j ◽

2018 ◽

Vol 8 (12) ◽

pp. 6242-6250 ◽

Cited By ~ 5

Author(s):

Yu-Ying Zhang ◽

Xiao-Le Li ◽

Tong-Yun Li ◽

Mei-Ying Li ◽

Ri-Ming Huang ◽

...

Keyword(s):

Oxidative Stress ◽

Propionic Acid ◽

Foam Cell ◽

Cell Formation ◽

Foam Cell Formation ◽

Macrophage Foam Cell ◽

Parent Molecule ◽

Microbial Metabolite ◽

Cd36 Expression

PCA2 and its major microbial metabolite HPPA inhibited macrophage foam cell formation, which may be due to regulating ABCA1, SR-B1 and CD36 expression, and restricted cellular oxidative stress and inflammation via NF-κB pathway.

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Effects of gut microbial metabolite trimethylamine N-oxide (TMAO) on platelets and endothelial cells

Clinical Hemorheology and Microcirculation ◽

10.3233/ch-209206 ◽

2020 ◽

Vol 76 (2) ◽

pp. 309-316

Author(s):

A. Krüger-Genge ◽

F. Jung ◽

F. Hufert ◽

E.-M. Jung ◽

J.-H. Küpper ◽

...

Keyword(s):

Endothelial Cells ◽

Cardiovascular Diseases ◽

Basic Research ◽

Intestinal Microbiome ◽

Food Conversion ◽

Microbial Metabolite ◽

Dietary Nutrients ◽

Key Players ◽

Underlying Causes ◽

Gut Metabolism

Thrombotic events result from different pathologies and are the underlying causes of severe diseases like stroke or myocardial infarction. Recent basic research now revealed a link between food uptake, food conversion and gut metabolism. Gut microbial production of trimethylamine N-oxide (TMAO) from dietary nutrients like choline, lecithin and L-carnitine was associated with the development of cardiovascular diseases. Within this review we give a systematic overview about the influence of TMAO on blood components like platelets and endothelial cells which both are involved as key players in thrombotic processes. In summary, a mechanistic correlation between the gut microbiome, TMAO and cardiovascular diseases becomes obvious and emphasizes to the significance of the intestinal microbiome.

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Endotoxin Alteration of the Mucopolysaccharide Blood Vessel Coating in Rats

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100050755 ◽

1974 ◽

Vol 32 ◽

pp. 148-149

Author(s):

D. E. Philpott ◽

A. Takahashi

Keyword(s):

Skeletal Muscle ◽

Endothelial Cells ◽

Salivary Gland ◽

Carotid Artery ◽

Basement Membrane ◽

Coronary Vessels ◽

Ruthenium Red ◽

E Coli ◽

Old Rats ◽

The Brain

Two month, eight month and two year old rats were treated with 10 or 20 mg/kg of E. Coli endotoxin I. P. The eight month old rats proved most resistant to the endotoxin. During fixation the aorta, carotid artery, basil arartery of the brain, coronary vessels of the heart, inner surfaces of the heart chambers, heart and skeletal muscle, lung, liver, kidney, spleen, brain, retina, trachae, intestine, salivary gland, adrenal gland and gingiva were treated with ruthenium red or alcian blue to preserve the mucopolysaccharide (MPS) coating. Five, 8 and 24 hrs of endotoxin treatment produced increasingly marked capillary damage, disappearance of the MPS coating, edema, destruction of endothelial cells and damage to the basement membrane in the liver, kidney and lung.

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Complex Vesicles, Microtubules, and Cytoplasmic Filaments in the Endothelial Cells of Normal Dog Aorta

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100100603 ◽

1968 ◽

Vol 26 ◽

pp. 172-173

Author(s):

C. N. Sun ◽

J. J. Ghidoni

Keyword(s):

Electron Microscopy ◽

Endothelial Cells ◽

Cross Sections ◽

Functional Significance ◽

Tubular Structures ◽

Aldehyde Fixation ◽

Cytoplasmic Filaments

Endothelial cells in longitudinal and cross sections of aortas from 3 randomly selected “normal” mongrel dogs were studied by electron microscopy. Segments of aorta were distended with cold cacodylate buffered 5% glutaraldehyde for 10 minutes prior to being cut into small, well oriented tissue blocks. After an additional 1-1/2 hour period in glutaraldehyde, the tissue blocks were well rinsed in buffer and post-fixed in OsO4. After dehydration they were embedded in a mixture of Maraglas, D.E.R. 732, and DDSA.Aldehyde fixation preserves the filamentous and tubular structures (300 Å and less) for adequate demonstration and study. The functional significance of filaments and microtubules has been recently discussed by Buckley and Porter; the precise roles of these cytoplasmic components remains problematic. Endothelial cells in canine aortas contained an abundance of both types of structures.

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Ultrastructural Alterations in Sinusoidal Endothelial Fenestrae as a Result of Hypoxia

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100090828 ◽

1976 ◽

Vol 34 ◽

pp. 168-169

Author(s):

Waykin Nopanitaya ◽

Raeford E. Brown ◽

Joe W. Grisham ◽

Johnny L. Carson

Keyword(s):

Endothelial Cells ◽

Experimental Model ◽

Hepatic Lobule ◽

Ultrastructural Alterations ◽

Large Type ◽

Sinusoidal Endothelial Fenestrae ◽

General Size ◽

Sem Studies

Mammalian endothelial cells lining hepatic sinusoids have been found to be widely fenestrated. Previous SEM studies (1,2) have noted two general size catagories of fenestrations; large fenestrae were distributed randomly while the small type occurred in groups. These investigations also reported that large fenestrae were more numerous and larger in the endothelial cells at the afferent ends of sinusoids or around the portal areas, whereas small fenestrae were more numerous around the centrilobular portion of the hepatic lobule. It has been further suggested that under some physiologic conditions small fenestrae could fuse and subsequently become the large type, but this is, as yet, unproven.We have used a reproducible experimental model of hypoxia to study the ultrastructural alterations in sinusoidal endothelial fenestrations in order to investigate the origin of occurrence of large fenestrae.

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Ultrastructural studies on the interaction of haemophilus influenzae with human endothelial cells in vitro

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010016073x ◽

1990 ◽

Vol 48 (3) ◽

pp. 636-637

Author(s):

D.J.P. Ferguson ◽

M. Virji ◽

H. Kayhty ◽

E.R. Moxon

Keyword(s):

Endothelial Cells ◽

Haemophilus Influenzae ◽

Intercellular Junctions ◽

Blood Stream ◽

Ultrastructural Studies ◽

Endothelial Barriers ◽

Serotype B ◽

Meningitis In Children ◽

Respiratory Epithelial

Haemophilus influenzae is a human pathogen which causes meningitis in children. Systemic H. influenzae infection is largely confined to encapsulated serotype b organisms and is a major cause of meningitis in the U.K. and elsewhere. However, the pathogenesis of the disease is still poorly understood. Studies in the infant rat model, in which intranasal challenge results in bacteraemia, have shown that H. influenzae enters submucosal tissues and disseminates to the blood stream within minutes. The rapidity of these events suggests that H. influenzae penetrates both respiratory epithelial and endothelial barriers with great efficiency. It is not known whether the bacteria penetrate via the intercellular junctions, are translocated within the cells or carried across the cellular barrier in 'trojan horse' fashion within phagocytes. In the present studies, we have challenged cultured human umbilical cord_vein endothelial cells (HUVECs) with both capsulated (b+) and capsule-deficient (b-) isogenic variants of one strain of H. influenzae in order to investigate the interaction between the bacteria and HUVEC and the effect of the capsule.

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