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

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.

scholarly journals POS1065 CIRCULATING ENDOTHELIAL CELLS AS A MARKER OF CARDIOVASCULAR DISEASES IN PATIENTS WITH PSORIATIC ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 811.1-811
Author(s):  
S. Smiyan ◽  
A. Bilukha ◽  
B. Koshak
Keyword(s):  
Endothelial Cells ◽  
Cardiovascular Risk ◽  
Psoriatic Arthritis ◽  
Cardiovascular Diseases ◽  
Endothelial Damage ◽  
Diagnostic Methods ◽  
Circulating Endothelial Cells ◽  
Control Group ◽  
Cardiovascular Morbidity And Mortality ◽  
Increased Risk

Background:Psoriatic arthritis (PsA) is a chronic inflammatory joint disease which develops in patients with psoriasis. Mortality among patients with PsA is 1.28 times higher than population levels and in most cases it is caused by cardio-vascular diseases (CVD). Those patients have increased risk of clinical and subclinical CVD, mostly due to endothelial dysfunction (ED) and accelerated atherosclerosis. Elevated levels of circulating endothelial cells (CEC) have been described in different cardiovascular pathologies, suggesting their potential use as diagnostic biomarkers for dysfunction of endothelium.Objectives:To identify the potential role of circulating endothelial cells as a marker of cardiovascular diseases in patients with psoriatic arthritis.Methods:In total, ninety-four patients with PsA, who fulfilled the disease criteria (CASPAR) were examined using standard diagnostic methods (including C-reactive protein (CRP), lipid profile) and evaluation endothelium-dependent vasodilation in response to reactive hyperemia (EDVD). Circulating endothelial cells were determined in the peripheral venous blood samples by flow cytometry and counted according to a standardized protocol using a fluorescence microscope after acridine orange labeling. The control group, which were consisted from thirty healthy adults were also examined.Results:CEC were quantified in patients with PsA (7,15 ± 0,19 cells mL−1) and in the control group (4,05 ± 0,11 cells mL−1). Comparing two groups of patients, endothelial circulating cell level was significantly different (p = 0.0001). Finally, we analyzed the relationship between CEC count, comorbidities, cardiovascular risk factors and EDVD in patients with PsA. Increased CEC levels were associated with obesity (r=0,62), duration of disease (r=0,65), age (r=0,67), increased CRP (r=0,76), high blood pressure (r=0,87) and decreased EDVD (r=–0,91).Conclusion:CEC counts were significantly higher in patients with PsA, positively correlated with the main factors of CVD, and another specific marker of ED - EDVD. Elevated CEC levels were also associated with high concentrations of CRP, which plays a direct role in promoting vascular inflammation, vessel damage and clinical CVD events. In conclusion, increased CEC counts provide a direct proof of endothelial damage in patient with PsA and a clinically informative diagnostic tool for endothelial damage in pre-symptomatic CVD. As CEC are one of the most sensitive biomarker for ED, further efforts should concentrate on improving the sensitivity of its detection in order to increase diagnostic sensitivity.References:[1]Maura Farinacci, Thomas Krahn, Wilfried Dinh, et al. Circulating endothelial cells as biomarker for cardiovascular diseases. Res Pract Thromb Haemost, Vol. 3, Issue, 2019, P.49-58;[2]C. Horreau, C. Pouplard, E. Brenautet, et al. Cardiovascular morbidity and mortality in psoriasis and psoriatic arthritis: a systematic literature review. J Eur Acad Dermatol Venereol, Vol. 27, Issue 3, 2013, P.12-19;[3]Frank Verhoeven, Clément Prati, Céline Demougeot, Daniel Wendling. Cardiovascular risk in psoriatic arthritis, a narrative review. Joint Bone Spine, Vol. 87, Issue 5, 2020, P.413-418;Disclosure of Interests:None declared.

scholarly journals Cytoprotective Role of Edible Seahorse (Hippocampus abdominalis)-Derived Peptides in H2O2-Induced Oxidative Stress in Human Umbilical Vein Endothelial Cells

Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 86
Author(s):  
Yunok Oh ◽  
Chang-Bum Ahn ◽  
Jae-Young Je
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Cardiovascular Diseases ◽  
Combination Treatment ◽  
Umbilical Vein ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Staining ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

Oxidative stress-induced endothelial dysfunction is strongly linked to the pathogenesis of cardiovascular diseases. A previous study revealed that seahorse hydrolysates ameliorated oxidative stress-mediated human umbilical vein endothelial cells (HUVECs) injury. However, the responsible compounds have not yet been identified. This study aimed to identify cytoprotective peptides and to investigate the molecular mechanism underlying the cytoprotective role in H2O2-induced HUVECs injury. After purification by gel filtration and HPLC, two peptides were sequenced by liquid chromatography-tandem mass spectrometry as HGSH (436.43 Da) and KGPSW (573.65 Da). The synthesized peptides and their combination (1:1 ratio) showed significant HUVECs protection effect at 100 μg/mL against H2O2-induced oxidative damage via significantly reducing intracellular reactive oxygen species (ROS). Two peptides and their combination treatment resulted in the increased heme oxygenase-1 (HO-1), a phase II detoxifying enzyme, through the activation of nuclear transcription factor-erythroid 2-related factor (Nrf2). Additionally, cell cycle and nuclear staining analysis revealed that two peptides and their combination significantly protected H2O2-induced cell death through antiapoptotic action. Two peptides and their combination treatment led to inhibit the expression of proapoptotic Bax, the release of cytochrome C into the cytosol, the activation of caspase 3 by H2O2 treatment in HUVECs, whereas antiapoptotic Bcl-2 expression was increased with concomitant downregulation of Bax/Bcl-2 ratio. Taken together, these results suggest that seahorse-derived peptides may be a promising agent for oxidative stress-related cardiovascular diseases.

scholarly journals Macrophages as Emerging Key Players in Mitochondrial Transfers

2021 ◽  
Vol 9 ◽  
Author(s):  
Yidan Pang ◽  
Changqing Zhang ◽  
Junjie Gao
Keyword(s):  
Cardiovascular Diseases ◽  
Metabolic Regulation ◽  
Inflammatory Diseases ◽  
Negative Influence ◽  
Immune Defense ◽  
The Body ◽  
Key Players ◽  
Current Therapies ◽  
Obesity And Cancer ◽  
Host Tissues

Macrophages are a group of heterogeneous cells widely present throughout the body. Under the influence of their specific environments, via both contact and noncontact signals, macrophages integrate into host tissues and contribute to their development and the functions of their constituent cells. Mitochondria are essential organelles that perform intercellular transfers to regulate cell homeostasis. Our review focuses on newly discovered roles of mitochondrial transfers between macrophages and surrounding cells and summarizes emerging functions of macrophages in transmitophagy, metabolic regulation, and immune defense. We also discuss the negative influence of mitochondrial transfers on macrophages, as well as current therapies targeting mitochondria in macrophages. Regulation of macrophages through mitochondrial transfers between macrophages and their surrounding cells is a promising therapy for various diseases, including cardiovascular diseases, inflammatory diseases, obesity, and cancer.

Oxidative stress and diabetic cardiovascular disorders: roles of mitochondria and NADPH oxidaseThis review is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.

2010 ◽  
Vol 88 (3) ◽  
pp. 241-248 ◽  
Author(s):  
Garry X. Shen
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endothelial Cells ◽  
Cardiovascular Diseases ◽  
Mitochondrial Dysfunction ◽  
Cardiovascular Complications ◽  
Hypoglycemic Agents ◽  
Diabetic Patients ◽  
Plasminogen Activator Inhibitor 1 ◽  
In Cells

Cardiovascular diseases are the predominant cause of death in patients with diabetes mellitus. Underlying mechanism for the susceptibility of diabetic patients to cardiovascular diseases remains unclear. Elevated oxidative stress was detected in diabetic patients and in animal models of diabetes. Hyperglycemia, oxidatively modified atherogenic lipoproteins, and advanced glycation end products are linked to oxidative stress in diabetes. Mitochondria are one of major sources of reactive oxygen species (ROS) in cells. Mitochondrial dysfunction increases electron leak and the generation of ROS from the mitochondrial respiratory chain (MRC). High levels of glucose and lipids impair the activities of MRC complex enzymes. NADPH oxidase (NOX) generates superoxide from NADPH in cells. Increased NOX activity was detected in diabetic patients. Hyperglycemia and hyperlipidemia increased the expression of NOX in vascular endothelial cells. Accumulated lines of evidence indicate that oxidative stress induced by excessive ROS production is linked to many processes associated with diabetic cardiovascular complications. Overproduction of ROS resulting from mitochondrial dysfunction or NOX activation is associated with uncoupling of endothelial nitric oxide synthase, which leads to reduced production of nitric oxide and endothelial-dependent vasodilation. Gene silence or inhibitor of NOX reduced oxidized or glycated LDL-induced expression of plasminogen activator inhibitor-1 in endothelial cells. Statins, hypoglycemic agents, and exercise may reduce oxidative stress in diabetic patients through the reduction of NOX activity or the improvement of mitochondrial function, which may prevent or postpone the development of cardiovascular complications.

Abstract P324: Unhealthy Diet and Air Pollution Compromise Human Cardiovascular Cell Functions: A First Mechanistic Analysis

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Niloofar Ale-Agha ◽  
Nicole Buechner ◽  
Ulrich Sydlik ◽  
Klaus Unfried ◽  
Joachim Altschmied ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cardiovascular Diseases ◽  
Carbon Black ◽  
Ultrafine Particles ◽  
Culture Media ◽  
Density Lipoprotein ◽  
Cell Functions ◽  
Unhealthy Diet ◽  
Cardiovascular Aging ◽  
The Impact

Diet and pollution are environmental factors known to compromise ″healthy cardiovascular aging″. The molecular consequences of the permanent burden for aging of the cardiovascular system are unknown, since they have never been examined in primary, adult human cells. Therefore, this study investigates the impact of unhealthy diet on aging-related signaling pathways of human, primary cardiovascular cells and of airborne particles on human endothelial cells, as several studies demonstrated that ultrafine particles can enter the circulation and thus may interact with endothelial cells directly. Nutrition health reports have shown that the diet in industrialized countries contains more than 100 mg/dl low density lipoprotein (LDL) and a too high fraction of monosaccharides, especially fructose, which is metabolized insulin-independently. Both components have been shown to increase the risk for cardiovascular diseases. To simulate unhealthy diet we supplemented cell culture media of human, primary endothelial cells (EC), smooth muscle cells (SMC) and cardiomyocytes (CM) with 100 mg/dl LDL and replaced 1/3 of the glucose with fructose for one week. This treatment did not induce cell death in any of the cell types. However, we observed increased senescence, loss of endothelial nitric oxide synthase and increased nuclear localization of Foxo3 in EC, increased proliferation in SMC and hypertrophy in CM. With respect to pollution we have used ultrafine carbon black particles (ufCB), one of the major constituents of industrial and exhaust emissions, in concentrations our vessels are constantly exposed to. These concentrations of ufCB are non-toxic and non-inflammatory for EC. Despite these missing immediate effects, ufCB dramatically reduced the S-NO content, a marker for NO-bioavailability in EC and increased reactive oxgen species formation. As a consequence, ufCB dramatically increased senescence of EC after two weeks. Thus, unhealthy diet and a high burden of ultrafine carbon black nanoparticles, to which we are exposed every day, seem to induce a ″cardiovascular aging″ phenotype and can lead to severe cardiovascular diseases.

Aspirin-triggered lipoxin A4 blocks reactive oxygen species generation in endothelial cells: A novel antioxidative mechanism

2007 ◽  
Vol 97 (01) ◽  
pp. 88-98 ◽  
Author(s):  
Christina Barja-Fidalgo ◽  
Vany Nascimento-Silva ◽  
Maria Arruda ◽  
Iolanda Fierro
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Cardiovascular Diseases ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Protective Role ◽  
Ros Generation ◽  
Oxygen Species ◽  
Lipoxin A4 ◽  
Pre Treatment

SummaryLipoxins and their aspirin-triggered carbon-15 epimers have emerged as mediators of key events in endogenous anti-inflammation and resolution. However, the implication of these novel lipid mediators on cardiovascular diseases such as hypertension, atherosclerosis, and heart failure has not been investigated. One of the major features shared by these pathological conditions is the increased production of reactive oxygen species (ROS) generated by vascular NAD(P)H oxidase activation. In this study, we have examined whether an aspirin-triggered lipoxin A4 analog (ATL-1) modulates ROS generation in endothelial cells (EC). Pre-treatment of EC with ATL-1 (1–100 nM) completely blocked ROS production triggered by different agents, as assessed by dihydrorhodamine 123 and hydroethidine. Furthermore, ATL-1 inhibited the phosphorylation and translocation of the cytosplamic NAD(P)H oxidase subunit p47phox to the cell membrane as well as NAD(P)H oxidase activity. Western blot and immunofluorescence microscopy analyses showed that ATL-1 (100 nM) impaired the redox-sensitive activation of the transcriptional factor NF-κB, a critical step in several events associated to vascular pathologies. These results demonstrate that ATL-1 suppresses NAD(P)H oxidase-mediated ROS generation in EC, strongly indicating that lipoxins may play a protective role against the development and progression of cardiovascular diseases.

scholarly journals Gut microbes in cardiovascular diseases and their potential therapeutic applications

2020 ◽  
Author(s):  
Ling Jin ◽  
Xiaoming Shi ◽  
Jing Yang ◽  
Yangyu Zhao ◽  
Lixiang Xue ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Therapeutic Potential ◽  
Scientific Evidence ◽  
Intestinal Microbiome ◽  
Complex Interplay ◽  
Gut Microbes ◽  
Genetic And Environmental Factors ◽  
Gut Microbial Community ◽  
Near Future ◽  
Multiple Chronic Diseases

Abstract Microbial ecosystem comprises a complex community in which bacteria interact with each other. The potential roles of the intestinal microbiome play in human health have gained considerable attention. The imbalance of gut microbial community has been looked to multiple chronic diseases. Cardiovascular diseases (CVDs) are leading causes of morbidity worldwide and are influenced by genetic and environmental factors. Recent advances have provided scientific evidence that CVD may also be attributed to gut microbiome. In this review, we highlight the complex interplay between microbes, their metabolites, and the potential influence on the generation and development of CVDs. The therapeutic potential of using intestinal microbiomes to treat CVD is also discussed. It is quite possible that gut microbes may be used for clinical treatments of CVD in the near future.

scholarly journals Evolving Role of Microparticles in the Pathophysiology of Endothelial Dysfunction

2013 ◽  
Vol 59 (8) ◽  
pp. 1166-1174 ◽  
Author(s):  
Fina Lovren ◽  
Subodh Verma
Keyword(s):  
Endothelial Cells ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Vascular Endothelial Cells ◽  
Current Knowledge ◽  
Early Event ◽  
Prognostic Information ◽  
Vascular Events ◽  
Wide Range

BACKGROUND Endothelial dysfunction is an early event in the development and progression of a wide range of cardiovascular diseases. Various human studies have identified that measures of endothelial dysfunction may offer prognostic information with respect to vascular events. Microparticles (MPs) are a heterogeneous population of small membrane fragments shed from various cell types. The endothelium is one of the primary targets of circulating MPs, and MPs isolated from blood have been considered biomarkers of vascular injury and inflammation. CONTENT This review summarizes current knowledge of the potential functional role of circulating MPs in promoting endothelial dysfunction. Cells exposed to different stimuli such as shear stress, physiological agonists, proapoptotic stimulation, or damage release MPs, which contribute to endothelial dysfunction and the development of cardiovascular diseases. Numerous studies indicate that MPs may trigger endothelial dysfunction by disrupting production of nitric oxide release from vascular endothelial cells and subsequently modifying vascular tone. Circulating MPs affect both proinflammatory and proatherosclerotic processes in endothelial cells. In addition, MPs can promote coagulation and inflammation or alter angiogenesis and apoptosis in endothelial cells. SUMMARY MPs play an important role in promoting endothelial dysfunction and may prove to be true biomarkers of disease state and progression.

scholarly journals HIV-Nef Protein Transfer to Endothelial Cells Requires Rac1 Activation and Leads to Endothelial Dysfunction Implications for Statin Treatment in HIV Patients

2019 ◽  
Vol 125 (9) ◽  
pp. 805-820 ◽  
Author(s):  
Sarvesh Chelvanambi ◽  
Samir K. Gupta ◽  
Xingjuan Chen ◽  
Bradley W. Ellis ◽  
Bernhard F. Maier ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Antiretroviral Therapy ◽  
Cardiovascular Diseases ◽  
Extracellular Vesicles ◽  
Reactive Oxygen ◽  
Statin Treatment ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Hiv Patients

Rationale: Even in antiretroviral therapy-treated patients, HIV continues to play a pathogenic role in cardiovascular diseases. A possible cofactor may be persistence of the early HIV response gene Nef, which we have demonstrated recently to persist in the lungs of HIV+ patients on antiretroviral therapy. Previously, we have reported that HIV strains with Nef, but not Nef-deleted HIV strains, cause endothelial proinflammatory activation and apoptosis. Objective: To characterize mechanisms through which HIV-Nef leads to the development of cardiovascular diseases using ex vivo tissue culture approaches as well as interventional experiments in transgenic murine models. Methods and Results: Extracellular vesicles derived from both peripheral blood mononuclear cells and plasma from HIV+ patient blood samples induced human coronary artery endothelial cells dysfunction. Plasma-derived extracellular vesicles from antiretroviral therapy+ patients who were HIV-Nef+ induced significantly greater endothelial apoptosis compared with HIV-Nef-plasma extracellular vesicles. Both HIV-Nef expressing T cells and HIV-Nef-induced extracellular vesicles increased transfer of cytosol and Nef protein to endothelial monolayers in a Rac1-dependent manner, consequently leading to endothelial adhesion protein upregulation and apoptosis. HIV-Nef induced Rac1 activation also led to dsDNA breaks in endothelial colony forming cells, thereby resulting in endothelial colony forming cell premature senescence and endothelial nitric oxide synthase downregulation. These Rac1-dependent activities were characterized by NOX2-mediated reactive oxygen species production. Statin treatment equally inhibited Rac1 inhibition in preventing or reversing all HIV-Nef-induction abnormalities assessed. This was likely because of the ability of statins to block Rac1 prenylation as geranylgeranyl transferase inhibitors were effective in inhibiting HIV-Nef-induced reactive oxygen species formation. Finally, transgenic expression of HIV-Nef in endothelial cells in a murine model impaired endothelium-mediated aortic ring dilation, which was then reversed by 3-week treatment with 5 mg/kg atorvastatin. Conclusions: These studies establish a mechanism by which HIV-Nef persistence despite antiretroviral therapy could contribute to ongoing HIV-related vascular dysfunction, which may then be ameliorated by statin treatment.

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