C-reactive protein promotes vascular endothelial dysfunction partly via activating adipose tissue inflammation in hyperlipidemic rabbits

2013 ◽  
Vol 168 (3) ◽  
pp. 2397-2403 ◽  
Author(s):  
YangXin Chen ◽  
XiaoQiao Wang ◽  
JingTing Mai ◽  
XiaoMiao Zhao ◽  
YongHong Liang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Endothelial Dysfunction ◽  
Vascular Endothelial ◽  
Adipose Tissue Inflammation ◽  
Vascular Endothelial Dysfunction ◽  
C Reactive Protein ◽  
Tissue Inflammation ◽  
Reactive Protein

Low-Grade Inflammation in Hemophilia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1115-1115
Author(s):  
Lynn M Knowles ◽  
Hermann Eichler ◽  
Jan Pilch
Keyword(s):  
Adipose Tissue ◽  
Blood Circulation ◽  
Prophylactic Treatment ◽  
Coagulation Factor ◽  
Low Grade ◽  
Adipose Tissue Inflammation ◽  
C Reactive Protein ◽  
Tissue Inflammation ◽  
Reactive Protein ◽  
Low Grade Inflammation

We previously showed that impaired clotting in hemophilia leads to a deficit in macrophage differentiation, which negatively affects critical regenerative macrophage functions such as clot infiltration and red blood cell phagocytosis. These data provide a functional basis for the delayed wound healing as well as protracted joint inflammation commonly observed in hemophiliacs and suggest that altered macrophage function is linked to the activation of the innate immune system. We, therefore, hypothesize that hemophiliacs suffer from chronic low-grade inflammation, which in turn can affect joint health, tissue regeneration and age-related ailments such as cardiovascular disease. For this study, we collected citrated blood from 48 adult male patients with hemophilia A or B with an average age of 36 years and a body mass index (BMI) of 27.7 kg/m2. The majority of patients had a residual FVIII/FIX activity < 1% (77%) and received prophylactic treatment (60%) with a recombinant or plasmatic coagulation factor concentrate. Approximately one-half of the patients had target joints or other bleeding events in the last 3 months and one-third of the patients had contracted HBV, HCV or HIV. For controls, we randomly recruited male blood donors (n = 60; age, 35.8 years; BMI, 27.0) from our blood donation center. To assess inflammation in hemophiliacs, we analyzed platelet-poor plasma from our main collective and a BMI-adjusted cohort using commercially available ELISA kits. The results showed a significant increase of two acute-phase proteins, C-reactive protein and leptin in hemophilia patients compared to healthy controls. Further analysis demonstrated that C-reactive protein and leptin expression inversely correlated with the residual clotting activity as both parameters were high in patients with severe Hemophilia A or B and comparatively low in patients with moderate to mild hemophilia. Of note, there was neither an increase of C-reactive protein or leptin in hemophilia patients with recent bleeding (< 3 month), arthropathy, chronic viral infection nor a decrease in patients with coagulation factor activity > 10% due to prophylactic treatment or recent replacement. Therefore, these data suggest a basic link between clotting deficiencies and chronic low-grade inflammation. Low-grade inflammation is maintained by adipokines, which originate from the adipose tissue and are modulated by a process known as adipose tissue inflammation. In addition to the upregulation of the pro-inflammatory leptin, we detected a significant down-regulation of the anti-inflammatory adiponectin in the plasma of hemophilia patients resulting in a markedly decreased adiponectin/leptin ratio. To enquire if the adipose tissue inflammation in hemophilia originates from gram-negative gut bacteria that translocate into the blood circulation, we also detected elevated plasma levels of lipopolysaccharide-binding protein and hepcidin in hemophilia patients. Together, these data support the concept that low-grade inflammation in hemophilia originates from lipopolysaccharide, which in turn causes adipose tissue inflammation. To test the hypothesis that low-grade inflammation in hemophilia is caused by decreased clotting activity, we collected blood from hemophilia B patients before and after transition from a conventional standard-half-life factor IX concentrate to a prophylactic therapy with an elongated half-life (EHL) FIX (Albutrepennonacog alfa, Idelvion®). Following up on the enhanced factor replacement after > 6 months, we observed a return of hepcidin plasma levels back to baseline values in healthy controls. The decreased hepcidin values from EHL FXI therapy correlated with healing of target joints suggesting that EHL FIX not only controls bleeding but also inflammation. Together, our data demonstrate a specific link between hemophilia and low-grade inflammation that appears to involve increased lipopolysaccharide levels in the blood circulation and subsequent adipose tissue inflammation. In addition, we present evidence that low-grade inflammation is the result of the underlying clotting deficit and that sustained normalization of the clotting deficit with EHL factors ameliorates inflammation. Disclosures Eichler: Novo Nordisk: Membership on an entity's Board of Directors or advisory committees. Pilch:CSL Behring: Other: Grants (investigator initiated), Speakers Bureau; ASPIRE Award/Pfizer: Other: Grants (investigator initiated); Bayer: Consultancy, Speakers Bureau; Roche: Consultancy.

Nutrient-Adjusted High-Fat Diet is Associated with Absence of Periepididymal Adipose Tissue Inflammation: Is there a Link with Adequate Micronutrient Levels?

2013 ◽  
Vol 83 (5) ◽  
pp. 299-310 ◽  
Author(s):  
Monica Yamada ◽  
Marina Maintinguer Norde ◽  
Maria C. Borges ◽  
Tatiane Mieko de Meneses Fujii ◽  
Patrícia Silva Jacob ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
Adipose Tissue Inflammation ◽  
C Reactive Protein ◽  
High Fat ◽  
Tissue Inflammation ◽  
Reactive Protein ◽  
Tnf Α

The aim of this study was to investigate the real impact of dietary lipids on metabolic and inflammatory response in rat white adipose tissue. Male healthy Wistar rats were fed ad libitum with a control diet (CON, n=12) or with an adjusted high-fat diet (HFD, n=12) for 12 weeks. Oral glucose and insulin tolerance tests were performed during the last week of the protocol. Plasma fatty acid, lipid profile, body adiposity, and carcass chemical composition were analyzed. Plasma concentration of leptin, adiponectin, C-reactive protein (CRP), TNF-α, IL-6, and monocyte chemotactic protein (MCP-1) was measured. Periepididymal adipose tissue was employed to evaluate TNF-α, MCP-1, and adiponectin gene expression as well as NF-κB pathway and AKT proteins. Isocaloric intake of the adjusted HFD did not induce hyperphagia, but promoted an increase in periepididymal (HFD = 2.94 ± 0.77 vs. CON = 1.99 ± 0.26 g/100 g body weight, p = 0.01) and retroperitoneal adiposity (HFD = 3.11 ± 0.81 vs. CON = 2.08 ± 0.39 g/100 g body weight, p = 0.01) and total body lipid content (HFD = 105.3 ± 20.8 vs. CON = 80.5 ± 7.6 g carcass, p = 0.03). Compared with control rats, HFD rats developed glucose intolerance (p=0.01), dyslipidemia (p = 0.02) and exhibited higher C-reactive protein levels in response to the HFD (HFD = 1002 ± 168 vs. CON = 611 ± 260 ng/mL, p = 0.01). The adjusted HFD did not affect adipokine gene expression or proteins involved in inflammatory signaling, but decreased AKT phosphorylation after insulin stimulation in periepididymal adipose tissue (p = 0.01). In this study, nutrient-adjusted HFD did not induce periepididymal adipose tissue inflammation in rats, suggesting that the composition of HFD differently modulates inflammation in rats, and adequate micronutrient levels may also influence inflammatory pathways.

scholarly journals Adipose tissue inflammation. Part 1. Morphological and functional manifestations

2009 ◽  
Vol 55 (4) ◽  
pp. 44-49 ◽  
Author(s):  
Viktor Shvarts
Keyword(s):  
Adipose Tissue ◽  
Chronic Inflammatory Disease ◽  
Adipose Tissue Inflammation ◽  
C Reactive Protein ◽  
Tissue Inflammation ◽  
Reactive Protein ◽  
The Metabolic Syndrome ◽  
Definition Of ◽  
And Shifts

The review describes a new pathomorphological phenomenon: adipose tissue inflammation (ATI) that develops in obesity and is characterized by cell infiltration, fibrosis, microcirculatory changes, a shift in adipokine secretion and adipose tissue metabolism, as well as blood accumulation of nonspecific inflammatory markers, such as C-reactive protein, fibrinogen, leukocytes, the level of which reflects the degree of the process. The changes in adipokine secretion and shifts in fat and carbohydrate metabolism, which are typical of ATI, favor the development of atherosclerosis, essential hypertension, type 2 diabetes, and the metabolic syndrome. ATI shows up as a connecting link between these diseases and obesity. The definition of obesity as a chronic inflammatory disease is justified.

scholarly journals Endothelial dysfunction occurs independently of adipose tissue inflammation and insulin resistance in ovariectomized Yucatan miniature-swine

Adipocyte ◽  
2017 ◽  
Vol 7 (1) ◽  
pp. 35-44 ◽  
Author(s):  
Thomas J. Jurrissen ◽  
T. Dylan Olver ◽  
Nathan C. Winn ◽  
Zachary I. Grunewald ◽  
Gabriela S. Lin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Endothelial Dysfunction ◽  
Adipose Tissue Inflammation ◽  
Miniature Swine ◽  
Tissue Inflammation

scholarly journals MARKERS OF ENDOTHELIAL DYSFUNCTION: PATHOGENETIC ROLE AND DIAGNOSTIC SIGNIFICANCE

2019 ◽  
Vol 64 (1) ◽  
pp. 34-41 ◽  
Author(s):  
T. V. Stepanova ◽  
A. N. Ivanov ◽  
N. E. Tereshkina ◽  
E. B. Popyhova ◽  
D. D. Lagutina
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Asymmetric Dimethylarginine ◽  
Vascular Endothelial ◽  
C Reactive Protein ◽  
Pathogenetic Role ◽  
Reactive Protein ◽  
Von Willebrand ◽  
Endothelial Growth Factor ◽  
Willebrand Factor

Endothelial dysfunction (ED) is considered one of the pathogenetic mechanisms of a whole range of diseases. Detection of specific biochemical markers in the blood is an effective way to ED diagnostics that characterize the vascular endothelium state. This review highlights the pathogenetic role of the factors synthesized by endotheliocytes whose level changes in biological fluids reflect violations of the endothelium basic physiological properties: vasomotor function, thromboresistance, angiogenesis regulation, barrier and adhesion functions. In particular, the participation of nitric oxide metabolites, asymmetric dimethylarginine, endothelin-1, metabolic products of arachidonic acid, von Willebrand factor, thrombomodulin, vascular endothelial growth factor, vasohibine-1 and adhesion molecules in the onset and development of ED are reviewed. The diagnostic significances of factors damaging endothelium, such as C-reactive protein, homocysteine and 8-hydroxy-2’-deoxyguanosine, are discussed. In addition, the literature data of recent years about the prospects of clinical implication the detection of the above-mentioned factors which indicates structural and functional endothelial cells damage are given. Particular attention is paid to the ED markers detection prognostic significance and the possibility of their practical use for the ED diagnosis. The search of literature for the current review was conducted in RSIC, CyberLeninka, Scopus, Web of Science, MedLine and PubMed databases from 2012 to 2018 using the following keywords: endothelial dysfunction, nitric oxide, asymmetric dimethylarginine, endothelin-1, prostacyclin, thromboxane A2, epoxyeicosatrienoic acids, von Willebrand factor, thrombomodulin, vascular endothelial growth factor, vasohibin-1, adhesive molecules, C-reactive protein, homocysteine, and 8-hydroxy-2-deoxyguanosine.

scholarly journals Biomarkers of endothelial dysfunction in cardiovascular diseases

2017 ◽  
Vol 70 (1-2) ◽  
pp. 53-57
Author(s):  
Sonja Smiljic ◽  
Milica Mijovic ◽  
Sladjana Savic
Keyword(s):  
Nitric Oxide ◽  
Extracellular Matrix ◽  
Vascular Endothelial Growth Factor ◽  
Endothelial Dysfunction ◽  
Adhesion Molecules ◽  
Vascular Endothelial ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Endothelial Growth Factor

Introduction. Endothelial dysfunction is the result of numerous infectious or noninfectious acute and chronic diseases, mechanical damage, hemodynamic imbalance and effects of certain drugs. Endothelial dysfunction can be assessed by determining biomarkers (adhesion molecules, inflammatory cytokines and growth factors, and noninvasive visualization biomarkers). Intercellular adhesion molecule-1 and vascular cellular adhesion molecule. Adhesion molecules mediate the interaction of cells with the extracellular matrix, as well as with other cells. It is shown that adhesion molecules and molecules of the extracellular matrix are markers of endothelial dysfunction and they are involved in the pathogenesis of atherosclerosis. P-selectin and E-selectin. Determination of these two mediators is important not only in the evaluation of endothelial damage in acute inflammation, but in other chronic non-infectious conditions such as atherosclerosis. C-reactive protein. C-reactive protein reduces the transcription of endothelial nitric oxide synthase at the level of the endothelial cells and ?destabilize? their messenger ribonucleic acid, thus leading to a reduction of the synthesis of nitric oxide, in the basal and stimulated conditions, which is significant for the development of endothelial dysfunction as a part of the formation of subclinical atherosclerosis. Vascular endothelial growth factor, fibrinogen and thrombomodulin. Vascular endothelial growth factor is a cytokine that stimulates angiogenesis for the purpose of revascularization of ischemic tissues, and mediates in a variety of functions of endothelial cells, including proliferation, migration, invasion, survival and permeability. Noninvasive visualization biomarkers. Determination of intima-media complex thickness and calcium score index by computed tomography are considered clinically reliable methods in prevention and early diagnosis of coronary artery disease and acute myocardial infarction, changing the basic concepts of prevention. Conclusion. At this point it is not easy to say what clinical significance are listed biomarkers of endothelial dysfunction in determining the risk for cardiovascular disease.

scholarly journals ROS Modulating Effects of Lingonberry (Vaccinium vitis-idaea L.) Polyphenols on Obese Adipocyte Hypertrophy and Vascular Endothelial Dysfunction

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 885
Author(s):  
Katarzyna Kowalska ◽  
Radosław Dembczyński ◽  
Agata Gołąbek ◽  
Mariola Olkowicz ◽  
Anna Olejnik
Keyword(s):  
Adipose Tissue ◽  
Endothelial Dysfunction ◽  
Umbilical Vein ◽  
Ros Generation ◽  
Vascular Endothelial ◽  
Vascular Endothelial Dysfunction ◽  
Enzyme Expression ◽  
Lipogenic Genes ◽  
Triglyceride Content ◽  
Umbilical Vein Endothelial Cells

Oxidative stress and dysregulated adipocytokine secretion accompanying hypertrophied adipose tissue induce chronic inflammation, which leads to vascular endothelial dysfunction. The present study investigated the ability of anthocyanin (ACN) and non-anthocyanin polyphenol (PP) fractions from lingonberry fruit to mitigate adipose tissue hypertrophy and endothelial dysfunction using 3T3-L1 adipocytes and human umbilical vein endothelial cells (HUVECs). This study showed that the PP fraction decreased intracellular ROS generation in hypertrophied adipocytes by enhancing antioxidant enzyme expression (SOD2) and inhibiting oxidant enzyme expression (NOX4, iNOS). Moreover, PP and ACN fractions reduced triglyceride content in adipocytes accompanied by downregulation of the expression of lipogenic genes such as aP2, FAS, and DAGT1. Treatment with both fractions modulated the mRNA expression and protein secretion of key adipokines in hypertrophied adipocytes. Expression and secretion of leptin and adiponectin were, respectively, down- and upregulated. Furthermore, PP and ACN fractions alleviated the inflammatory response in TNF-α-induced HUVECs by inhibiting the expression of pro-inflammatory genes (IL-6, IL-1β) and adhesion molecules (VCAM-1, ICAM-1, SELE). The obtained results suggest that consuming polyphenol-rich lingonberry fruit may help prevent and treat obesity and endothelial dysfunction due to their antioxidant and anti-inflammatory actions.

Flavonoids in adipose tissue inflammation and atherosclerosis: one arrow, two targets

2020 ◽  
Vol 134 (12) ◽  
pp. 1403-1432 ◽  
Author(s):  
Manal Muin Fardoun ◽  
Dina Maaliki ◽  
Nabil Halabi ◽  
Rabah Iratni ◽  
Alessandra Bitto ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fruits And Vegetables ◽  
Metabolic Diseases ◽  
Therapeutic Agents ◽  
Adipose Tissue Inflammation ◽  
Cellular Mechanisms ◽  
Tissue Inflammation ◽  
Cholesterol Levels ◽  
Naturally Occurring ◽  
Pro Inflammatory Cytokines

Abstract Flavonoids are polyphenolic compounds naturally occurring in fruits and vegetables, in addition to beverages such as tea and coffee. Flavonoids are emerging as potent therapeutic agents for cardiovascular as well as metabolic diseases. Several studies corroborated an inverse relationship between flavonoid consumption and cardiovascular disease (CVD) or adipose tissue inflammation (ATI). Flavonoids exert their anti-atherogenic effects by increasing nitric oxide (NO), reducing reactive oxygen species (ROS), and decreasing pro-inflammatory cytokines. In addition, flavonoids alleviate ATI by decreasing triglyceride and cholesterol levels, as well as by attenuating inflammatory mediators. Furthermore, flavonoids inhibit synthesis of fatty acids and promote their oxidation. In this review, we discuss the effect of the main classes of flavonoids, namely flavones, flavonols, flavanols, flavanones, anthocyanins, and isoflavones, on atherosclerosis and ATI. In addition, we dissect the underlying molecular and cellular mechanisms of action for these flavonoids. We conclude by supporting the potential benefit for flavonoids in the management or treatment of CVD; yet, we call for more robust clinical studies for safety and pharmacokinetic values.

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