scholarly journals Circulating Endothelial Microparticles: A Key Hallmark of Atherosclerosis Progression

Scientifica ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Keshav Raj Paudel ◽  
Nisha Panth ◽  
Dong-Wook Kim
Keyword(s):  
Vascular Function ◽  
Cell Activation ◽  
Vascular Inflammation ◽  
Rho Kinase ◽  
Disease Status ◽  
Endothelial Microparticles ◽  
Atherosclerosis Progression ◽  
Mitogen Activated Protein ◽  
Circulating Microparticles ◽  
Ros Formation

The levels of circulating microparticles (MPs) are raised in various cardiovascular diseases. Their increased level in plasma is regarded as a biomarker of alteration in vascular function. The prominent MPs present in blood are endothelial microparticles (EMPs) described as complex submicron (0.1 to 1.0 μm) vesicles like structure, released in response to endothelium cell activation or apoptosis. EMPs possess both physiological and pathological effects and may promote oxidative stress and vascular inflammation. EMPs release is triggered by inducer like angiotensin II, lipopolysaccharide, and hydrogen peroxide leading to the progression of atherosclerosis. However, there are multiple physiological pathways for EMPs generation like NADPH oxidase derived endothelial ROS formation, Rho kinase pathway, and mitogen-activated protein kinases. Endothelial dysfunction is a key initiating event in atherosclerotic plaque formation. Atheroemboli, resulting from ruptured carotid plaques, is a major cause of stroke. Increasing evidence suggests that EMPs play an important role in the pathogenesis of cardiovascular disease, acting as a marker of damage, either exacerbating disease progression or triggering a repair response. In this regard, it has been suggested that EMPs have the potential to act as biomarkers of disease status. This review aims to provide updated information of EMPs in relation to atherosclerosis pathogenesis.

Red wine extract, resveratrol, on maintenance of organ function following trauma-hemorrhage

2012 ◽  
Vol 2 (10) ◽  
pp. 351
Author(s):  
Fu-Chao Liu ◽  
Huang-Ping Yu
Keyword(s):  
Intracellular Signaling ◽  
Red Wine ◽  
Antioxidant Properties ◽  
Neutrophil Function ◽  
Protective Effects ◽  
Organ Function ◽  
Mitogen Activated Protein ◽  
Ros Formation ◽  
Anti Inflammatory ◽  
And Control

Resveratrol, is a polyphenol that can be extracted from grapes and red wine, possess potential anti-inflammatory effects, which would result in the reduction of cytokine production, the alteration of the expression of adhesion molecule molecules, and the inhibition of neutrophil function. Resveratrol might also act as an antioxidant, anti-aging, and control of cell cycle and apoptosis. Resveratrol has been shown to have protective effects for patients in shock-like states. Such protective phenomenon is reported to be implicated in a variety of intracellular signaling pathways including the regulation of the mitogen-activated protein kinases (MAPK)/ hemeoxygenase-1 (HO-1) pathway, activates estrogen receptor (ER), and the mediation of pro-inflammatory cytokines, reactive oxygen species (ROS) formation and reactive. Moreover, through anti-inflammatory effects and antioxidant properties, the resveratrol is believed to maintain organ function following trauma-hemorrhage.Key words: resveratrol, anti-inflammatory, trauma-hemorrhage.

Osteoprotegerin and Osteopontin Serum Levels are Associated with Vascular Function and Inflammation in Coronary Artery Disease Patients

2020 ◽  
Vol 18 (5) ◽  
pp. 523-530 ◽  
Author(s):  
Konstantinos Maniatis ◽  
Gerasimos Siasos ◽  
Evangelos Oikonomou ◽  
Manolis Vavuranakis ◽  
Marina Zaromytidou ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Endothelial Function ◽  
Vascular Function ◽  
Serum Levels ◽  
Atherosclerosis Progression ◽  
Control Subjects ◽  
Significant Difference ◽  
Artery Disease ◽  
Stable Cad

Background: Osteoprotegerin and osteopontin have recently emerged as key factors in both vascular remodelling and atherosclerosis progression. Interleukin-6 (IL-6) is an inflammatory cytokine with a key role in atherosclerosis. The relationship of osteoprotegerin, osteopontin, and IL-6 serum levels with endothelial function and arterial stiffness was evaluated in patients with coronary artery disease (CAD). Methods: We enrolled 219 patients with stable CAD and 112 control subjects. Osteoprotegerin, osteopontin and IL-6 serum levels were measured using an ELISA assay. Endothelial function was evaluated by flow-mediated dilation (FMD) in the brachial artery and carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. Results: There was no significant difference between control subjects and CAD patients according to age and sex. Compared with control subjects, CAD patients had significantly impaired FMD (p<0.001) and increased PWV (p=0.009). CAD patients also had significantly higher levels of osteoprotegerin (p<0.001), osteopontin (p<0.001) and IL-6 (p=0.03), compared with control subjects. Moreover, IL-6 levels were correlated with osteoprotegerin (r=0.17, p=0.01) and osteopontin (r=0.30, p<0.001) levels. FMD was correlated with osteoprotegerin levels independent of possible confounders [b coefficient= - 0.79, 95% CI (-1.54, -0.05), p=0.04]. Conclusion: CAD patients have increased osteoprotegerin, osteopontin and IL-6 levels. Moreover, there is a consistent association between osteoprotegerin and osteopontin serum levels, vascular function and inflammation in CAD patients. These findings suggest another possible mechanism linking osteoprotegerin and osteopontin serum levels with CAD progression through arterial wall stiffening and inflammation.

scholarly journals GLP-1 Analog Liraglutide Improves Vascular Function in Polymicrobial Sepsis by Reduction of Oxidative Stress and Inflammation

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1175
Author(s):  
Johanna Helmstädter ◽  
Karin Keppeler ◽  
Franziska Aust ◽  
Leonie Küster ◽  
Katie Frenis ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vascular Function ◽  
Vascular Inflammation ◽  
Cecal Ligation ◽  
Isometric Tension ◽  
Polymicrobial Sepsis ◽  
Dot Blot ◽  
Markers Of Inflammation ◽  
Anti Inflammatory ◽  
And Oxidative Stress

Sepsis causes high mortality in the setting of septic shock. LEADER and other trials revealed cardioprotective and anti-inflammatory properties of glucagon-like peptide-1 (GLP-1) analogs like liraglutide (Lira). We previously demonstrated improved survival in lipopolysaccharide (LPS)-induced endotoxemia by inhibition of GLP-1 degradation. Here we investigate the effects of Lira in the polymicrobial sepsis model of cecal ligation and puncture (CLP). C57BL/6J mice were intraperitoneally injected with Lira (200 µg/kg/d; 3 days) and sepsis induced by CLP after one day of GLP-1 analog treatment. Survival and body temperature were monitored. Aortic vascular function (isometric tension recording), protein expression (immunohistochemistry and dot blot) and gene expression (qRT-PCR) were determined. Endothelium-dependent relaxation in the aorta was impaired by CLP and correlated with markers of inflammation (e.g., interleukin 6 and inducible nitric oxide synthase) and oxidative stress (e.g., 3-nitrotyrosine) was higher in septic mice, all of which was almost completely normalized by Lira therapy. We demonstrate that the GLP-1 analog Lira ameliorates sepsis-induced endothelial dysfunction by the reduction of vascular inflammation and oxidative stress. Accordingly, the findings suggest that the antioxidant and anti-inflammatory effects of GLP-1 analogs may be a valuable tool to protect the cardiovascular system from dysbalanced inflammation in polymicrobial sepsis.

Abstract 2474: Rho-Kinase Inhibition Improves Endothelium-Dependent Vasodilation during Hyperinsulinemia in Patients with Metabolic Syndrome

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Francesca Schinzari ◽  
Manfredi Tesauro ◽  
Valentina Rovella ◽  
Augusto Veneziani ◽  
Nadia Mores ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Vascular Function ◽  
Vascular Reactivity ◽  
Rho Kinase ◽  
Serine Phosphorylation ◽  
No Donor ◽  
Kinase Inhibition ◽  
Impaired Insulin

Impaired insulin-mediated vasodilation in the skeletal muscle may be involved in the development of hypertension in patients with metabolic syndrome (MetS) and contribute to insulin resistance by diminishing the glucose uptake. Rho-kinase, an effector of the small G protein Rho A, plays an important role in hypertension and is reported to interfere with insulin signaling through serine phosphorylation of insulin receptor substrate-1 in blood vessels. We therefore examined the role of Rho-kinase in the pathophysiology of impaired vascular reactivity in patients with MetS by evaluating the effect of Rho-kinase inhibition on NO-dependent vasodilation during hyperinsulinemia. Forearm blood flow (FBF) responses to acetylcholine (ACh), a stimulus for endothelial release of NO, and sodium nitroprusside (SNP), an exogenous NO donor, were assessed during insulin administration (0.1 mU/Kg/min) using the forearm perfusion technique in patients with MetS (n=10) and matched controls (n=10). Patients with MetS were then randomized to intra-arterial infusion of either fasudil (inhibitor of Rho-kinase, 200 μg/min) or placebo and reactivity to ACh and SNP was reassessed. During hyperinsulinemia, vasodilator responses to both ACh and SNP were blunted in patients with MetS (both P>0.001 vs. controls). In patients who received fasudil, its administration did not change unstimulated FBF (P=0.75 vs. insulin alone); the vasodilator response to ACh, however, was significantly enhanced by fasudil (P=0.009 vs. insulin alone), while the response to SNP was not significantly changed (P=0.56). In patients with MetS who received placebo, vascular reactivity to both ACh and SNP was not different than before (both P>0.05). In conclusion, Rho-kinase inhibition during hyperinsulinemia improves endothelium-dependent vasodilator responsiveness in patients with MetS. This suggests that, under those conditions, intravascular activation of Rho-kinase is involved in the pathophysiology of endothelial dysfunction and may constitute a critical mediator linking metabolic and hemodynamic abnormalities in insulin resistance. As a consequence, targeting Rho-kinase might beneficially impact both vascular function and insulin sensitivity in patients with MetS.

Pharmacological modulation of procoagulant microparticles improves haemodynamic dysfunction during septic shock in rats

2014 ◽  
Vol 111 (01) ◽  
pp. 154-164 ◽  
Author(s):  
Su-Emmanuelle Degirmenci ◽  
Fatiha Zobairi ◽  
Asael Berger ◽  
Grégory Meyer ◽  
Mélanie Burban ◽  
...  
Keyword(s):  
Septic Shock ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Vascular Dysfunction ◽  
Vascular Inflammation ◽  
Activated Protein C ◽  
Resistance Arteries ◽  
Pharmacological Modulation ◽  
Circulating Microparticles ◽  
Haemodynamic Improvement

SummaryCirculating microparticles play a pro-inflammatory and procoagulant detrimental role in the vascular dysfunction of septic shock. It was the objective of this study to investigate mechanisms by which a pharmacological modulation of microparticles could affect vascular dysfunction in a rat model of septic shock. Septic or sham rats were treated by activated protein C (aPC) and resuscitated during 4 hours. Their microparticles were harvested and inoculated to another set of healthy recipient rats. Haemodynamic parameters were monitored, circulating total procoagulant microparticles assessed by prothrombinase assay, and their cell origin characterised. Mesenteric resistance arteries, aorta and heart were harvested for western blotting analysis. We found that a) the amount and phenotype of circulating microparticles were altered in septic rats with an enhanced endothelial, leucocyte and platelet contribution; b) aPC treatment significantly reduced the generation of leucocyte microparticles and norepinephrine requirements to reach the mean arterial pressure target in septic rats; c) Microparticles from untreated septic rats, but not from aPC-treated ones, significantly reduced the healthy recipients’ mean arterial pressure; d) Microparticle thromboxane content and aPC activity were significantly increased in aPC-treated septic rats. In inoculated naïve recipients, microparticles from aPC-treated septic rats prompted reduced NF-κB and cyclooxygenase-2 arterial activation, blunted the generation of pro-inflammatory iNOS and secondarily increased platelet and endothelial microparticles. In conclusion, in this septic shock model, increased circulating levels of procoagulant microparticles led to negative haemodynamic outcomes. Pharmacological treatment by aPC modified the cell origin and levels of circulating microparticles, thereby limiting vascular inflammation and favouring haemodynamic improvement.

scholarly journals Elevated antiviral, myeloid and endothelial inflammatory markers in severe COVID-19

2020 ◽  
Author(s):  
Ryan S Thwaites ◽  
Ashley Sanchez Sevilla Uruchurtu ◽  
Matthew Siggins ◽  
Felicity Liew ◽  
Clark D Russell ◽  
...  
Keyword(s):  
Lung Injury ◽  
Cell Activation ◽  
Vascular Inflammation ◽  
Endothelial Cell Activation ◽  
Gm Csf ◽  
Cytokine Levels ◽  
Angiopoietin 2 ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Host Inflammatory Response

Introductory paragraphThe mechanisms that underpin COVID-19 disease severity, and determine the outcome of infection, are only beginning to be unraveled. The host inflammatory response contributes to lung injury, but circulating mediators levels fall below those in classical ‘cytokine storms’. We analyzed serial plasma samples from 619 patients hospitalized with COVID-19 recruited through the prospective multicenter ISARIC clinical characterization protocol U.K. study and 39 milder community cases not requiring hospitalization. Elevated levels of numerous mediators including angiopoietin-2, CXCL10, and GM-CSF were seen at recruitment in patients who later died. Markers of endothelial injury (angiopoietin-2 and von-Willebrand factor A2) were detected early in some patients, while inflammatory cytokines and markers of lung injury persisted for several weeks in fatal COVID-19 despite decreasing antiviral cytokine levels. Overall, markers of myeloid or endothelial cell activation were associated with severe, progressive, and fatal disease indicating a central role for innate immune activation and vascular inflammation in COVID-19.

scholarly journals The Vascular Side of Chronic Bed Rest: When a Therapeutic Approach Becomes Deleterious

2020 ◽  
Vol 9 (4) ◽  
pp. 918 ◽  
Author(s):  
Anna Pedrinolla ◽  
Alessandro L. Colosio ◽  
Roberta Magliozzi ◽  
Elisa Danese ◽  
Emine Kirmizi ◽  
...  
Keyword(s):  
Blood Flow ◽  
Shear Rate ◽  
Vascular Function ◽  
Inflammatory Markers ◽  
Near Infrared ◽  
Vastus Lateralis ◽  
Vascular Inflammation ◽  
Bed Rest ◽  
Total Hemoglobin ◽  
No Bioavailability

The interplay between chronic constraint and advanced aging on blood flow, shear-rate, vascular function, nitric oxide (NO)-bioavailability, microcirculation, and vascular inflammation factors is still a matter of debate. Ninety-eight individuals (Young, n = 28, 23 ± 3 yrs; Old, n = 36, 85 ± 7 yrs; Bedridden, n = 34, 88 ± 6 yrs) were included in the study. The bedridden group included old individuals chronically confined to bed (3.8 ± 2.3 yrs). A blood sample was collected and analyzed for plasma nitrate, and vascular inflammatory markers. Hyperemic response (∆peak) during the single passive leg movement (sPLM) test was used to measure vascular function. Skeletal muscle total hemoglobin was measured at the vastus lateralis during the sPLM test, by means of near infrared spectroscopy (NIRS). Bedridden subjects revealed a depletion of plasma nitrates compared with Old (−23.8%) and Young (−31.1%). Blood flow was lower in the Bedridden in comparison to Old (−20.1%) and Young (−31.7%). Bedridden presented lower sPLM ∆peak compared Old (−72.5%) and the Young (−83.3%). ∆peak of NIRS total hemoglobin was lower in the Bedridden compared to that in the Young (−133%). All vascular inflammatory markers except IL-6 were significantly worse in the Bedridden compared to Old and Young. No differences were found between the Old and Young in inflammatory markers. Results of this study confirm that chronic physical constraint induces an exacerbation of vascular disfunction and differential regulation of vascular-related inflammatory markers. The mechanisms involved in these negative adaptations seems to be associated with endothelial dysfunction and consequent diminished NO-bioavailability likely caused by the reduced shear-rate consequential to long-term reduction of physical activity.

scholarly journals Receptor Heterodimerization and Co-Receptor Engagement in TLR2 Activation Induced by MIC1 and MIC4 from Toxoplasma gondii

2019 ◽  
Vol 20 (20) ◽  
pp. 5001 ◽  
Author(s):  
Flávia Costa Mendonça-Natividade ◽  
Carla Duque Lopes ◽  
Rafael Ricci-Azevedo ◽  
Aline Sardinha-Silva ◽  
Camila Figueiredo Pinzan ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Transforming Growth Factor Beta ◽  
Cell Activation ◽  
Cytokine Production ◽  
Transforming Growth Factor ◽  
Protein Complexes ◽  
Transmembrane Protein ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Carbohydrate Recognition Domains

The microneme organelles of Toxoplasma gondii tachyzoites release protein complexes (MICs), including one composed of the transmembrane protein MIC6 plus MIC1 and MIC4. In this complex, carbohydrate recognition domains of MIC1 and MIC4 are exposed and interact with terminal sialic acid and galactose residues, respectively, of host cell glycans. Recently, we demonstrated that MIC1 and MIC4 binding to the N-glycans of Toll-like receptor (TLR) 2 and TLR4 on phagocytes triggers cell activation and pro-inflammatory cytokine production. Herein, we investigated the requirement for TLR2 heterodimerization and co-receptors in MIC-induced responses, as well as the signaling molecules involved. We used MICs to stimulate macrophages and HEK293T cells transfected with TLR2 and TLR1 or TLR6, both with or without the co-receptors CD14 and CD36. Then, the cell responses were analyzed, including nuclear factor-kappa B (NF-κB) activation and cytokine production, which showed that (1) only TLR2, among the studied factors, is crucial for MIC-induced cell activation; (2) TLR2 heterodimerization augments, but is not critical for, activation; (3) CD14 and CD36 enhance the response to MIC stimulus; and (4) MICs activate cells through a transforming growth factor beta-activated kinase 1 (TAK1)-, mammalian p38 mitogen-activated protein kinase (p38)-, and NF-κB-dependent pathway. Remarkably, among the studied factors, the interaction of MIC1 and MIC4 with TLR2 N-glycans is sufficient to induce cell activation, which promotes host protection against T. gondii infection.

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