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Journal articles on the topic 'Anti-thrombotic Molecules'

Author: Grafiati

Published: 6 September 2023

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1

Péč, Martin Jozef, Jakub Benko, Jakub Jurica, et al. "The Anti-Thrombotic Effects of PCSK9 Inhibitors." Pharmaceuticals 16, no. 9 (2023): 1197. http://dx.doi.org/10.3390/ph16091197.

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Atherosclerosis is the primary process that underlies cardiovascular disease. The connection between LDL cholesterol and the formation of atherosclerotic plaques is established by solid evidence. PCSK9 inhibitors have proven to be a valuable and practical resource for lowering the LDL cholesterol of many patients in recent years. Their inhibitory effect on atherosclerosis progression seems to be driven not just by lipid metabolism modification but also by LDL-independent mechanisms. We review the effect of PCSK9 inhibitors on various mechanisms involving platelet activation, inflammation, endo

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2

De Meyer, Simon. "ADAMTS13, an Anti-thrombotic Protein: Evidence Outside of Thrombotic Thrombocytopenic Purpura." Blood 134, Supplement_1 (2019): SCI—41—SCI—41. http://dx.doi.org/10.1182/blood-2019-121114.

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von Willebrand factor (VWF) is a large multimeric plasma glycoprotein that plays a crucial role in hemostasis and thrombosis. VWF recruits platelets at sites of vascular injury by acting as a molecular bridge between circulating platelets and the site of injured or activated blood vessels. Biosynthesis of VWF is restricted to endothelial cells and megakaryocytes. Endothelial VWF is constitutively secreted into plasma and subendothelium, or is stored as "ultra-large" (UL)-VWF multimers in endothelial Weibel-Palade bodies. VWF produced in megakaryocytes is packaged as UL-VWF in the a-granules of

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3

Fuentes, Eduardo, and Iván Palomo. "Extracellular ATP metabolism on vascular endothelial cells: A pathway with pro-thrombotic and anti-thrombotic molecules." Vascular Pharmacology 75 (December 2015): 1–6. http://dx.doi.org/10.1016/j.vph.2015.05.002.

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4

Muro, S., and V. Muzykantov. "Targeting of Antioxidant and Anti-Thrombotic Drugs to Endothelial Cell Adhesion Molecules." Current Pharmaceutical Design 11, no. 18 (2005): 2383–401. http://dx.doi.org/10.2174/1381612054367274.

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5

Zaki, Magdi E. A., Sami A. Al-Hussain, Vijay H. Masand, Manoj K. Sabnani, and Abdul Samad. "Mechanistic and Predictive QSAR Analysis of Diverse Molecules to Capture Salient and Hidden Pharmacophores for Anti-Thrombotic Activity." International Journal of Molecular Sciences 22, no. 15 (2021): 8352. http://dx.doi.org/10.3390/ijms22158352.

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Thrombosis is a life-threatening disease with a high mortality rate in many countries. Even though anti-thrombotic drugs are available, their serious side effects compel the search for safer drugs. In search of a safer anti-thrombotic drug, Quantitative Structure-Activity Relationship (QSAR) could be useful to identify crucial pharmacophoric features. The present work is based on a larger data set comprising 1121 diverse compounds to develop a QSAR model having a balance of acceptable predictive ability (Predictive QSAR) and mechanistic interpretation (Mechanistic QSAR). The developed six para

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6

Shiels, Katie, Alexandros Tsoupras, Ronan Lordan, et al. "Bioactive Lipids of Marine Microalga Chlorococcum sp. SABC 012504 with Anti-Inflammatory and Anti-Thrombotic Activities." Marine Drugs 19, no. 1 (2021): 28. http://dx.doi.org/10.3390/md19010028.

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Microalgae are at the start of the food chain, and many are known producers of a significant amount of lipids with essential fatty acids. However, the bioactivity of microalgal lipids for anti-inflammatory and antithrombotic activities have rarely been investigated. Therefore, for a sustainable source of the above bioactive lipids, the present study was undertaken. The total lipids of microalga Chlorococcum sp., isolated from the Irish coast, were fractionated into neutral-, glyco-, and phospho-lipids, and were tested in vitro for their anti-inflammatory and antithrombotic activities. All test

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7

Shiels, Katie, Alexandros Tsoupras, Ronan Lordan, et al. "Bioactive Lipids of Marine Microalga Chlorococcum sp. SABC 012504 with Anti-Inflammatory and Anti-thrombotic Activities." Marine Drugs 19, no. 1 (2021): 28. http://dx.doi.org/10.3390/md19010028.

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Microalgae are at the start of the food chain, and many are known producers of a significant amount of lipids with essential fatty acids. However, the bioactivity of microalgal lipids for anti-inflammatory and antithrombotic activities have rarely been investigated. Therefore, for a sustainable source of the above bioactive lipids, the present study was undertaken. The total lipids of microalga Chlorococcum sp., isolated from the Irish coast, were fractionated into neutral-, glyco-, and phospho-lipids, and were tested in vitro for their anti-inflammatory and antithrombotic activities. All test

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8

Clemetson, Jeannine, and Kenneth Clemetson. "Platelet GPIb complex as a target for anti-thrombotic drug development." Thrombosis and Haemostasis 99, no. 03 (2008): 473–79. http://dx.doi.org/10.1160/th07-12-0718.

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SummarySpecific inhibition of platelet function is a major target of antithrombotic drug research. Platelet receptors are both accessible and specific but have multiple functions often linked to a wide range of ligands. GPIb complex is best known as a major platelet receptor for vonWillebrand factor essential for platelet adhesion under high shear conditions found in arteries and in thrombosis. Recent animal studies have supported inhibition of GPIb as a good candidate for anti-thrombotic drug development with several classes of proteins showing important specific effects and the required disc

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9

Bălașa, Adrian Florian, Cristina Chircov, and Alexandru Mihai Grumezescu. "Marine Biocompounds for Neuroprotection—A Review." Marine Drugs 18, no. 6 (2020): 290. http://dx.doi.org/10.3390/md18060290.

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While terrestrial organisms are the primary source of natural products, recent years have witnessed a considerable shift towards marine-sourced biocompounds. They have achieved a great scientific interest due to the plethora of compounds with structural and chemical properties generally not found in terrestrial products, exhibiting significant bioactivity ten times higher than terrestrial-sourced molecules. In addition to the antioxidant, anti-thrombotic, anti-coagulant, anti-inflammatory, anti-proliferative, anti-hypertensive, anti-diabetic, and cardio-protection properties, marine-sourced bi

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10

Lopez, Jose J., Mohammed El Haouari, Isaac Jardin, et al. "Flavonoids and Platelet-Derived Thrombotic Disorders." Current Medicinal Chemistry 26, no. 39 (2019): 7035–47. http://dx.doi.org/10.2174/0929867325666180417170218.

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: Thrombotic disorders are characterized by an increase in the probability of the formation of unnecessary thrombi that might be due to the activation of the coagulation cascade or the circulating platelets. Platelets or thrombocytes play an essential role in hemostasis but abnormal platelet function leads to the development of a number of cardiovascular complications, including thrombotic disorders. Under pathological conditions, platelets are associated with the development of different thrombotic disorders, including atherosclerosis, arterial thrombosis and stroke, deep venous thrombosis an

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11

Wautier, Jean-Luc, Pierre Gane, Wassim El Nemer, Jean-Dider Rain, Caroline Le Van Kim, and Marie-Paule Wautier. "Increased Adhesion of Red Blood Cells from Patients with Polycythemia Vera Is Mediated by Lu/B-CAM and Laminin alpha 5." Blood 106, no. 11 (2005): 3527. http://dx.doi.org/10.1182/blood.v106.11.3527.3527.

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Abstract Polycythemia vera (PV) is associated to a high risk of vascular thrombosis which is related to red blood cell (RBC) volume and platelet activation. We have investigated whether, beside high hematocrit, RBCs exhibit qualitative abnormalities. Along this line we have measured RBC adhesion to human umbilical vein endothelial cell (HUVEC) under static and flow conditions. A group of 38 PV patients and one of 36 normal subjects were explored. Adhesion molecule expression using specific antibodies (anti-CD36, CD49d, ICAM-4, Lu/B-CAM, CD147, CD47) and flow cytometry were determined on RBCs.

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12

Varga, Zsuzsa. "Cardioprotective role of omega-3 polyunsaturated fatty acids." Orvosi Hetilap 149, no. 14 (2008): 627–37. http://dx.doi.org/10.1556/oh.2008.28296.

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Cardioprotective action of omega-3 polyunsaturated fatty acids such as eicosapentaenoic and docosahexaenoic acid in fish and α-linolenic acid in plants was demonstrated in primary and secondary clinical trials. Fish oil therapy causes a marked decrease in serum triacylglycerol and very low density lipoprotein levels and increases moderately high density lipoprotein levels without any adverse effects. Omega-3 fatty acids decrease slightly, but significantly blood pressure, enhance endothelial function, they have anti-aggregator, anti-thrombotic and anti-inflammatory effects as well. These benef

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13

Schaller, Monica, Sabine Hiltbrunner, Irmela Sulzer, et al. "Anti-idiotypic small molecules neutralize pathogenic anti-ADAMTS13 autoantibodies in autoimmune Thrombotic Thrombocytopenic Purpura in vitro - new treatment tools in vivo? (P5173)." Journal of Immunology 190, no. 1_Supplement (2013): 68.14. http://dx.doi.org/10.4049/jimmunol.190.supp.68.14.

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Abstract A therapy aiming at neutralization of inhibitory autoantibodies (Abs) causing autoimmune thrombotic thrombocytopenic purpura (aTTP) would be highly desirable. We screened a large combinatorial small protein library of Designed-Ankryin-Repeat-Protein (DARPins, Molecular Partners AG, Switzerland; library size 1015-23) for anti-idiotypic binders to an equimolar pool of three spleen-derived inhibitory anti-ADAMTS13 monoclonal Abs of two aTTP patients containing 1 of 4 shared CDR3 motifs. Four unique anti-idiotypic DARPins were purified and their neutralization potential tested against 8 s

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14

Solitano, Virginia, Gionata Fiorino, Ferdinando D’Amico, Laurent Peyrin-Biroulet, and Silvio Danese. "Thrombosis in IBD in the Era of JAK Inhibition." Current Drug Targets 22, no. 1 (2020): 126–36. http://dx.doi.org/10.2174/1389450121666200902164240.

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: Patients with inflammatory bowel diseases (IBD) have an increased risk of thrombosis. The interaction between inflammation and coagulation has been extensively studied. It is well-known that some drugs can influence the haemostatic system, but several concerns on the association between therapies and increased risk of thrombosis remain open. While biologics seem to have a protective role against thrombosis via their anti-inflammatory effect, some concerns about an increased risk of thrombosis with JAK inhibitors have been raised. We conducted a literature review to assess the association bet

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15

Allen, Kristi L., Mukesh K. Jain, and Keith R. McCrae. "KLF2 and KLF4 Are Essential Mediators of the Anti-Thrombotic Effects of Statins in the Presence of Antiphospholipid/Anti-ß2GPI Antibodies,." Blood 118, no. 21 (2011): 3272. http://dx.doi.org/10.1182/blood.v118.21.3272.3272.

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Abstract Abstract 3272 Antiphospholipid syndrome (APS) is characterized by thrombosis and/or recurrent pregnancy loss in the presence of antiphospholipid antibodies (APLA). The majority of APLA are directed against phospholipid binding proteins, particularly β2GPI. Anti-ß2GPI antibodies activate endothelial cells and monocytes in a β2GPI-dependent manner through a pathway that involves NF-κB and leads to increased expression of adhesion molecules, tissue factor and proinflammatory cytokines. Krüppel-like factors (KLFs) regulate endothelial cell and monocyte responses to inflammatory stimuli;

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16

Bhavika Kunwar, Vartika Jain, and Surendra Kumar Verma. "Qualitative phytochemical screening and in vitro thrombolytic activity of Capparis decidua Edgew. Fruit." GSC Biological and Pharmaceutical Sciences 19, no. 3 (2022): 160–67. http://dx.doi.org/10.30574/gscbps.2022.19.3.0232.

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Abnormal thrombosis plays an important role in development of ischemic heart disease and stroke. Synthetic thrombolytic agents are effective but possess some adverse effects. Therefore, the need for development of comparatively safer anti-thrombotic drugs from natural resources such as plants arises. Capparis decidua Edgew. (Family – Capparaceae) is a densely branched, xerophytic shrub and grows abundantly in arid and semiarid regions. Its fruits are major ingredient of the popular ‘Panchkuta’ vegetable of Rajasthan and also used to prepare pickle. Caper fruits are recommended for treatment of

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17

Magamedov, I. D., L. P. Pivovarova, S. P. Nokhrin, et al. "Factors of inflammatory, adhesiveness and thrombosis in acute lower limb ischemia and dexamethasone therapy." Russian Journal of Immunology 25, no. 3 (2022): 251–58. http://dx.doi.org/10.46235/1028-7221-1117-foi.

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Lymphocyte-to-platelet adhesion during hypoxia, tissue damage, activation of inflammation and coagulation is associated with expression of ICAM-1 membrane molecules by blood and tissue cells. At the same time, the platelet adhesion receptors determine their adherence to endothelium and recruited lymphocytes. Moreover, the role of platelets in pathogenesis of ischemic cardiovascular diseases comprises their ability to modulate both hemostasis and inflammatory reactions, which are accompanied by secretion of inflammatory mediators and some factors that promote recruitment of leukocytes to tissue

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18

Wagener, Frank A. D. T. G., Peter Pickkers, Stephen J. Peterson, Stephan Immenschuh, and Nader G. Abraham. "Targeting the Heme-Heme Oxygenase System to Prevent Severe Complications Following COVID-19 Infections." Antioxidants 9, no. 6 (2020): 540. http://dx.doi.org/10.3390/antiox9060540.

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SARS-CoV-2 is causing a pandemic resulting in high morbidity and mortality. COVID-19 patients suffering from acute respiratory distress syndrome (ARDS) are often critically ill and show lung injury and hemolysis. Heme is a prosthetic moiety crucial for the function of a wide variety of heme-proteins, including hemoglobin and cytochromes. However, injury-derived free heme promotes adhesion molecule expression, leukocyte recruitment, vascular permeabilization, platelet activation, complement activation, thrombosis, and fibrosis. Heme can be degraded by the anti-inflammatory enzyme heme oxygenase

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19

Ivanov, Daniil G., Son N. Ngyuen, Si-Hung Le, et al. "Structure of pathogenic anti-PF4 autoantibodies reveals the mechanism of immune response formation in vaccine-induced thrombotic thrombocytopenia (VITT)." Journal of Immunology 210, no. 1_Supplement (2023): 234.07. http://dx.doi.org/10.4049/jimmunol.210.supp.234.07.

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Abstract Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe, but rare, side effect of adenoviral-vectored COVID-19 vaccines. It is attributed to formation of autoantibodies recognizing Platelet Factor 4 (PF4) and capable of triggering platelet activation, which leads to thrombosis. We used mass spectrometry (MS) to determine the structure of a VITT patient-derived anti-PF4 antibodies (VITT IgG) and identified their unique properties underlying pathogenicity. The VITT IgGs studied in this work were extracted from the plasma of a ChAdOx1 vaccine recipient, who developed VITT.

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20

Ucci, F. M., F. Villani, A. Capozzi та ін. "AB0127 ANTIGENIC ASSESSMENT FOR THE Β2GPIOX-PF4 COMPLEX IN A MONOCENTRIC COHORT OF PATIENTS WITH APS, THROMBOSIS DURING SARS-COV-2 INFECTION AND VITT". Annals of the Rheumatic Diseases 82, Suppl 1 (2023): 1243.1–1243. http://dx.doi.org/10.1136/annrheumdis-2023-eular.6134.

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BackgroundPlatelet factor 4 (PF4) is a protein with a pro-clotting function expressed by activated platelets with a high affinity for anionic glycosaminoglycans present on the platelet surface. It has been shown that the positively charged surface of PF4 tetramer interacts with the negatively charged regions of β2glycoprotein I (β2GPI) domains, stabilising the link between the antigen and the phospholipid surface, thus increasing the possibility of binding with the respective antibodies. In particular, a tetramer of PF4 selectively binds two molecules of β2GPI, favouring the dimerization of th

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21

Caso, Francesco, Luisa Costa, Donato Rigante, et al. "Biological Treatments in Behçet’s Disease: Beyond Anti-TNF Therapy." Mediators of Inflammation 2014 (2014): 1–14. http://dx.doi.org/10.1155/2014/107421.

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Behçet’s disease (BD) is universally recognized as a multisystemic inflammatory disease of unknown etiology with chronic course and unpredictable exacerbations: its clinical spectrum varies from pure vasculitic manifestations with thrombotic complications to protean inflammatory involvement of multiple organs and tissues. Treatment has been revolutionized by the progressed knowledge in the pathogenetic mechanisms of BD, involving dysfunction and oversecretion of multiple proinflammatory molecules, chiefly tumor necrosis factor- (TNF-)α, interleukin- (IL-) 1β, and IL-6. However, although biolog

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22

Nozaki, Kazuya, Hiroaki Hikiami, Hirozo Goto, Takako Nakagawa, Naotoshi Shibahara, and Yutaka Shimada. "Keishibukuryogan (Gui-Zhi-Fu-Ling-Wan), a Kampo Formula, Decreases Disease Activity and Soluble Vascular Adhesion Molecule-1 in Patients with Rheumatoid Arthritis." Evidence-Based Complementary and Alternative Medicine 3, no. 3 (2006): 359–64. http://dx.doi.org/10.1093/ecam/nel025.

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An increasing death rate due to cardiovascular disease in patients with rheumatoid arthritis (RA) has been reported. Keishibukuryogan (KBG) is a traditional Chinese/Japanese (Kampo) formula that has been administered to patients with blood stagnation, e.g. thrombotic disease and atherosclerosis. The objective of this study was to evaluate the efficacy of KBG on disease activity and endothelial dysfunction in RA patients. Sixteen RA patients were enrolled and administered KBG (12 g per day) for 12 weeks in addition to continuing other drugs. The disease activity of RA was assessed by modified d

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23

Sturgeon, Sharelle A., Catherine Jones, James A. Angus, and Christine E. Wright. "Adaptation of the Folts and electrolytic methods of arterial thrombosis for the study of anti-thrombotic molecules in small animals." Journal of Pharmacological and Toxicological Methods 53, no. 1 (2006): 20–29. http://dx.doi.org/10.1016/j.vascn.2005.06.006.

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24

Wang, Chaoming, Mengrou Chen, Xiaoyu Lu, et al. "Isolation and Characterization of Poeciguamerin, a Peptide with Dual Analgesic and Anti-Thrombotic Activity from the Poecilobdella manillensis Leech." International Journal of Molecular Sciences 24, no. 13 (2023): 11097. http://dx.doi.org/10.3390/ijms241311097.

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When Poecilobdella manillensis attacks its prey, the prey bleeds profusely but feels little pain. We and other research teams have identified several anticoagulant molecules in the saliva of P. manillensis, but the substance that produces the paralyzing effect in P. manillensis is not known. In this study, we successfully isolated, purified, and identified a serine protease inhibitor containing an antistasin-like domain from the salivary secretions of P. manillensis. This peptide (named poeciguamerin) significantly inhibited elastase activity and slightly inhibited FXIIa and kallikrein activit

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25

Schaller, Monica, Sabine Hiltbrunner, Irmela Sulzer, et al. "High-Throughput Screening of a Large Combinatorial Library of Small Proteins Against Human Spleen-Derived Monoclonal Anti-ADAMTS13 Antibodies Yields Specific Anti-Idiotypic Molecules – Potential Tools for New Treatment Strategy in Acquired TTP." Blood 120, no. 21 (2012): 487. http://dx.doi.org/10.1182/blood.v120.21.487.487.

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Abstract Abstract 487 Background. Acquired Thrombotic Thrombocytopenic Purpura (TTP) is the result of autoantibodies (Abs) neutralizing and/or accelerating clearance of ADAMTS13. Despite the first-line treatment with daily plasma exchange (PEX), acute TTP is still associated with a mortality rate of ∼20% leaving survivors at high risk of relapse. Availability of molecules for neutralization of pathogenic anti-ADAMTS13 Abs during acute bouts as well as for the targeted elimination of anti-ADAMTS13 specific memory B- and plasma-cells to prevent relapses are thus highly desirable tools to improve

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26

Jayakumar, Thanasekaran, Chun-Ming Yang, Ting-Lin Yen та ін. "Anti-Inflammatory Mechanism of An Alkaloid Rutaecarpine in LTA-Stimulated RAW 264.7 Cells: Pivotal Role on NF-κB and ERK/p38 Signaling Molecules". International Journal of Molecular Sciences 23, № 11 (2022): 5889. http://dx.doi.org/10.3390/ijms23115889.

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Lipoteichoic acid (LTA) is a key cell wall component and virulence factor of Gram-positive bacteria. LTA contributes a major role in infection and it mediates inflammatory responses in the host. Rutaecarpine, an indolopyridoquinazolinone alkaloid isolated from Evodia rutaecarpa, has shown a variety of fascinating biological properties such as anti-thrombotic, anticancer, anti-obesity and thermoregulatory, vasorelaxing activity. It has also potent effects on the cardiovascular and endocrine systems. Herein, we investigated rutaecarpine’s (Rut) anti-inflammatory effects in LTA-stimulated RAW mac

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27

Stark, Júlia. "Oxidatív stressz és atherosclerosis." Orvosi Hetilap 156, no. 28 (2015): 1115–19. http://dx.doi.org/10.1556/650.2015.30201.

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Atherosclerosis is a leading cause of death in developed countries. Genetic susceptibility and environmental factors play a role in the pathogenesis. Most of these factors lead to endothelial dysfunction and other pro-atherogenic processes by causing oxidative stress. Atherosclerosis typically develops at the curved and branched regions of the arterial tree, where the laminar blood flow is disturbed. This leads to increased permeability of the endothel to low density lipoprotein molecules, which accumulate in the intima and are oxidised by vascular cells. Oxidised low density lipoprotein takes

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28

Lamendola, R., P. Favia, F. Palumbo, and R. d'Agostino. "Plasma-modification of polymers: process control in PE-CVD of gas-barrier films and plasma-processes for immobilizing anti-thrombotic molecules." European Physical Journal Applied Physics 4, no. 1 (1998): 65–71. http://dx.doi.org/10.1051/epjap:1998244.

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29

Huang, Mei-Zhou, Xiao-Rong Lu, Ya-Jun Yang, Xi-Wang Liu, Zhe Qin, and Jian-Yong Li. "Cellular Metabolomics Reveal the Mechanism Underlying the Anti-Atherosclerotic Effects of Aspirin Eugenol Ester on Vascular Endothelial Dysfunction." International Journal of Molecular Sciences 20, no. 13 (2019): 3165. http://dx.doi.org/10.3390/ijms20133165.

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Aspirin eugenol ester (AEE) possesses anti-thrombotic, anti-atherosclerotic and anti-oxidative effects. The study aims to clarify the mechanism underlying the anti-atherosclerotic effects of AEE on vascular endothelial dysfunction. Both the high-fat diet (HFD)-induced atherosclerotic rat model and the H2O2-induced human umbilical vein endothelial cells (HUVECs) model were used to investigate the effects of AEE on vascular endothelial dysfunction. UPLC/QTOF-MS coupled with a multivariate data analysis method were used to profile the variations in the metabolites of HUVECs in response to differe

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30

Badimon, Lina, Cristina Rodríguez, María González-Díez, and José Martínez-González. "Sphingosine-1-phosphate: A bioactive lipid that confers high-density lipoprotein with vasculoprotection mediated by nitric oxide and prostacyclin." Thrombosis and Haemostasis 101, no. 04 (2009): 665–73. http://dx.doi.org/10.1160/th08-10-0675.

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SummarySphingosine-1-phosphate (S1P) is a bioactive lipid generated in the intracellular membranes from the metabolism of sphingomyelin. Once secreted/exported by cells of haematopoietic origin and vascular cells S1P interacts with plasma proteins and accumulates in high-density lipoprotein (HDL). Growing evidence indicates that HDL-associated S1P is responsible for the beneficial effects of these lipoproteins on vasorelaxation, cell survival, cell adhesiveness, angiogenesis and synthesis of two powerful endogenous anti-atherogenic and anti-thrombotic molecules such as nitric oxide (NO) and pr

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Maevskaya, Marina V., Yulia V. Kotovskaya, Vladimir T. Ivashkin, et al. "The National Consensus statement on the management of adult patients with non-alcoholic fatty liver disease and main comorbidities." Terapevticheskii arkhiv 94, no. 2 (2022): 216–53. http://dx.doi.org/10.26442/00403660.2022.02.201363.

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The National Consensus was prepared with the participation of the National Medical Association for the Study of the Multimorbidity, Russian Scientific Liver Society, Russian Association of Endocrinologists, Russian Association of Gerontologists and Geriatricians, National Society for Preventive Cardiology, Professional Foundation for the Promotion of Medicine Fund PROFMEDFORUM. The aim of the multidisciplinary consensus is a detailed analysis of the course of non-alcoholic fatty liver disease (NAFLD) and the main associated conditions. The definition of NAFLD is given, its prevalence is

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Navarrete, Ana-Maria, Caterina Casari, Paulette Legendre, et al. "A murine model to characterize the antithrombotic effect of molecules targeting human von Willebrand factor." Blood 120, no. 13 (2012): 2723–32. http://dx.doi.org/10.1182/blood-2012-03-420042.

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Abstractvon Willebrand factor (VWF) is a promising target for developing antithrombotic drugs. The absence of accessible animal models impedes the study of specific human VWF (huVWF) targeting molecules in thrombosis. huVWF is not functional in the mouse because of a lack of interaction between huVWF and murine glycoprotein Ib. Using site-directed mutagenesis, we have replaced single or multiple amino acids in huVWF with their murine counterparts to eliminate species incompatibility. Using hydrodynamic injection, we have expressed the different chimeric VWF constructs into VWF−/− mice. Only hu

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33

Flax, Sherri. "ADAMTS13 Immunohistochemical Expression in Normal and Diseased Equine Tissues." Blood 134, Supplement_1 (2019): 4925. http://dx.doi.org/10.1182/blood-2019-127407.

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ADAMTS13 is a metallopeptidase primarily synthesized in the liver. Its main function is to cleave von Willebrand factor (VWF) on the endothelial surface, and thus regulate platelet adhesion at the sites of vascular injury; VWF acts as a scaffold at the site of injury for platelet activation, platelet binding, and clot formation. Platelet activation also results in the release of platelet-dense granule components (such as cytokines, pro- and anti-inflammatory factors and other bioactive molecules) that are essential regulators of coagulation, but are also associated with inflammation. Reduced a

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Schaller, Monica M., Monique Vogel, Magdalena Skowronska, Irmela Sulzer, and Johanna A. Kremer Hovinga Strebel. "Anti-Idiotypic-Designed-Ankyrin-Repeat-Molecules (DARPins) Universally Neutralize Plasma-Derived Autoantibodies in Acquired TTP Patients." Blood 126, no. 23 (2015): 104. http://dx.doi.org/10.1182/blood.v126.23.104.104.

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Abstract Background. Autoantibodies (Abs) neutralizing and/or accelerating clearance of the von Willebrand factor-cleaving protease-ADAMTS13 are the major culprits in acquired Thrombotic Thrombocytopenic Purpura (aTTP). Despite the first-line treatment with daily plasma exchange (PEX), acute aTTP is still today associated with a mortality rate of ~20% leaving survivors at high risk of relapse. To improve patient care and/or treatment of aTTP we explored the capacity of anti-idiotypic small molecules to specifically bind and potentially neutralize pathogenic anti-ADAMTS13 autoantibodies thereby

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Zhao, Aizhi, Chunsheng Li, George Coukos, Don L. Siegel, and Nathalie Scholler. "Isolation of high affinity human scFv antibodies against mouse and human tumor endothelial marker 1 (TEM1) using yeast-display scFv library derived from an autoimmune patient. (42.4)." Journal of Immunology 182, no. 1_Supplement (2009): 42.4. http://dx.doi.org/10.4049/jimmunol.182.supp.42.4.

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Abstract TEM1 is predominantly expressed on neovasculature, thus ideally suited for targeted imaging and therapy for cancer. Yeast has emerged as an alternative technology for display and selection of recombinant antibody fragments (scFv). Because autoimmune disorders may produce self-reactive specificities, an autoimmune repertoire derived from a patient with thrombotic thrombocytopenic purpura (TTP) was screened to isolate anti-TEM1 scFv. A yeast-display scFv library was constructed by homologous recombination of the TTP patient repertoire originally expressed on M13 bacteriophage. The libra

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Jang, Hyosun, Seo-Young Kwak, Sunhoo Park, et al. "Pravastatin Alleviates Radiation Proctitis by Regulating Thrombomodulin in Irradiated Endothelial Cells." International Journal of Molecular Sciences 21, no. 5 (2020): 1897. http://dx.doi.org/10.3390/ijms21051897.

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Although radiotherapy plays a crucial in the management of pelvic tumors, its toxicity on surrounding healthy tissues such as the small intestine, colon, and rectum is one of the major limitations associated with its use. In particular, proctitis is a major clinical complication of pelvic radiotherapy. Recent evidence suggests that endothelial injury significantly affects the initiation of radiation-induced inflammation. The damaged endothelial cells accelerate immune cell recruitment by activating the expression of endothelial adhesive molecules, which participate in the development of tissue

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Ishii, Kazuyoshi, Shosaku Nomura, Tomoki Ito, et al. "Recombinant Thrombomodurin For The Treatment Of Transplantation-Associated Coagulopathy After Allogeneic Stem Cell Transplantation." Blood 122, no. 21 (2013): 5454. http://dx.doi.org/10.1182/blood.v122.21.5454.5454.

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Abstract Background Levels of cytokines, chemokines and soluble molecules fluctuate after allogeneic hematopoietic stem cell transplantation (HSCT). These biomarkers are possible to be a diagnostic and prognostic value for transplantation-associated coagulopathy (TAC). In the present study, we investigated the effects of recombinant thrombomodulin (rTM) on levels of the cytokines, chemokines, and soluble factors registered in the ‘SIGHT’ research. SIGHT comprises the capital letters of five complications after HSCT, namely sinusoidal obstruction syndrome (SOS same as VOD), infection, GVHD, hem

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Natalucci, F., A. Di Filippo, F. Ceccarelli, et al. "AB0119 ROLE OF COSTIMULATORY MOLECULES IN SYSTEMIC LUPUS ERYTHEMATOSUS: FOCUS ON CD137." Annals of the Rheumatic Diseases 81, Suppl 1 (2022): 1190–91. http://dx.doi.org/10.1136/annrheumdis-2022-eular.3813.

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BackgroundSystemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by a wide autoantibodies production. The traditionally concept of a B-cell driven disease has been changed in the last years due to the evidence demonstrating the crucial role of T cells in SLE pathogenesis. In particular, regulatory (Treg) and memory T cells seem act through co-stimulatory and co-inhibitory molecules, such as CD137, PD1-1 and CTLA4. The over-expression of this molecules on lymphocytes may contribute to immune system dysregulation.ObjectivesThe primary objective of the present case-contr

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Aggarwal, Anu, Courtney L. Jennings, Emily Manning, and Scott J. Cameron. "Platelets at the Vessel Wall in Non-Thrombotic Disease." Circulation Research 132, no. 6 (2023): 775–90. http://dx.doi.org/10.1161/circresaha.122.321566.

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Platelets are small, anucleate entities that bud from megakaryocytes in the bone marrow. Among circulating cells, platelets are the most abundant cell, traditionally involved in regulating the balance between thrombosis (the terminal event of platelet activation) and hemostasis (a protective response to tissue injury). Although platelets lack the precise cellular control offered by nucleate cells, they are in fact very dynamic cells, enriched in preformed RNA that allows them the capability of de novo protein synthesis which alters the platelet phenotype and responses in physiological and path

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Welles, E. G., C. Bourne, J. W. Tyler, and M. K. Boudreaux. "Detection of Activated Feline Platelets in Platelet-rich Plasma by Use of Fluorescein-labeled Antibodies and Flow Cytometry." Veterinary Pathology 31, no. 5 (1994): 553–60. http://dx.doi.org/10.1177/030098589403100507.

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Platelets contribute to prethrombotic or thrombotic states; however, accepted evaluation methods (i.e., in vitro testing by use of an aggregometer) of platelet function in cats can be difficult because of the large volume of blood required from which platelets are isolated and the potential for platelet activation due to difficult venipunctures in sometimes uncooperative or excited animals. The activation problem also contributes to errors in platelet counts. Platelets from four domestic short haired cats (two males, two females, 2–3 years old) minimally restrained without sedation or anesthes

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De Ceunynck, Karen E. P., Christian G. Peters, Sharjeel A. Chaudhry, et al. "A Chemical APC Mimetic Protects Endothelium from Thromboinflammatory Injury." Blood 128, no. 22 (2016): 3835. http://dx.doi.org/10.1182/blood.v128.22.3835.3835.

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Abstract Stimulation of protease-activated receptor 1 (PAR1) on endothelium by activated protein C (APC) is protective in animal models of inflammation and APC has been used clinically in sepsis and wound healing. Clinical use of APC in sepsis, however, was terminated as it was compromised by APC's anticoagulant activity, which is associated with bleeding and limits its dosing in patients. We used a small molecule approach to circumvent this problem. With support from the Molecular Libraries Program, we screened 302,457 compounds to identify small molecules that modulated PAR1-mediated platele

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Bertani, Fabio, Dalila Di Francesco, Maria Dolores Corrado, Maria Talmon, Luigia Grazia Fresu, and Francesca Boccafoschi. "Paracrine Shear-Stress-Dependent Signaling from Endothelial Cells Affects Downstream Endothelial Function and Inflammation." International Journal of Molecular Sciences 22, no. 24 (2021): 13300. http://dx.doi.org/10.3390/ijms222413300.

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Cardiovascular diseases (CVDs), mainly ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and major contributors to disability worldwide. Despite their heterogeneity, almost all CVDs share a common feature: the endothelial dysfunction. This is defined as a loss of functionality in terms of anti-inflammatory, anti-thrombotic and vasodilatory abilities of endothelial cells (ECs). Endothelial function is greatly ensured by the mechanotransduction of shear forces, namely, endothelial wall shear stress (WSS). Low WSS is associated with endothelial dysfunction, repres

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Totzeck, Matthias, Raluca-Ileana Mincu, Simone Mrotzek, Dirk Schadendorf, and Tienush Rassaf. "Cardiovascular diseases in patients receiving small molecules with anti-vascular endothelial growth factor activity: A meta-analysis of approximately 29,000 cancer patients." European Journal of Preventive Cardiology 25, no. 5 (2018): 482–94. http://dx.doi.org/10.1177/2047487318755193.

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Background Targeted therapy with tyrosine kinase inhibitors with anti-vascular endothelial growth factor activity improves survival of cancer patients. Cardiovascular complications are critical and it is unknown whether these require specific treatment strategies. We aimed to clarify the associated risk of cardiovascular adverse events in patients treated with tyrosine kinase inhibitors. Design The design of this study was a meta-analysis of randomised controlled trials. Methods We searched PubMed, Cochrane, EMBASE and Web of Science databases for randomised controlled trials published until J

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Sullenger, Bruce A. "Aptamers as Rapid Onset and Rapidly Reversible Antithrombotic Agents." Blood 134, Supplement_1 (2019): SCI—16—SCI—16. http://dx.doi.org/10.1182/blood-2019-121056.

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Clinical evaluation of our factor IXa RNA aptamer in two thousand patients undergoing percutaneous coronary intervention has demonstrated that aptamers can rapidly and potently inhibit their target proteins in patients and that antidote molecules can rapidly and precisely control such activity in the minute time frame. These observations suggest that aptamers represent useful molecules to tightly control biochemical processes in humans in real time. To begin to explore this potential further, we have started to evaluate the utility of antidote-mediated control of aptamers for a variety of othe

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Pankratenko, T. E., O. V. Moskalets, and T. Yu Abaseeva. "SOLUBLE ADHESION MOLECULES IN CHILDREN WITH HEMOLYTIC UREMIC SYNDROME." Medical Immunology (Russia) 20, no. 6 (2018): 871–76. http://dx.doi.org/10.15789/1563-0625-2018-6-871-876.

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Atypical hemolytic uremic syndrom (aHUS) is a rare severe life-threatening form of thrombotic microangiopathy. aHUS is thought to be primarily mediated by dysfunctional complement regulation, due to mutations or genetic rearrangement of the complement components, or regulatory factors, as well as autoantibody production to the complement factors. These alterations promote uncontrolled complement activation by the alternative pathway on the surface of endothelial cells, followed by endothelial dysfunction, microthrombosis and organ damage, especially, renal pathology. Many studies showed that t

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Patiño-Trives, A. M., C. Perez-Sanchez, A. Ibañez-Costa, et al. "OP0038 SPLICEOSOME ALTERATIONS IN LEUCOCYTES FROM APS, SLE AND SLE+APS PATIENTS ARE CLOSELY RELATED TO THEIR MAIN CLINICAL FEATURES." Annals of the Rheumatic Diseases 80, Suppl 1 (2021): 20.2–20. http://dx.doi.org/10.1136/annrheumdis-2021-eular.2485.

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Background:To date, although multiple molecular approaches have illustrated the various aspects of Primary Antiphospholipid Syndrome (APS), systemic lupus erythematosus (SLE) and antiphospholipid syndrome plus lupus (APS plus SLE), no study has so far fully characterized the potential role of posttranscriptional regulatory mechanisms such as the alternative splicing.Objectives:To identify shared and differential changes in the splicing machinery of immune cells from APS, SLE and APS plus SLE patients, and their involvement in the activity and clinical profile of these autoimmune disorders.Meth

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Rehani, Teena, Adria Jonas та Arne Slungaard. "The Major Phagocyte Peroxidase-Derived Oxidant HOSCN Stimulates Gene-Specific p38 MAPK- Dependent, NF-κb-Mediated Activation of Tissue Factor, VCAM-1 and ICAM-1 Expression In Endothelium." Blood 116, № 21 (2010): 1481. http://dx.doi.org/10.1182/blood.v116.21.1481.1481.

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Abstract Abstract 1481 Thiocyanate (SCN-) is, unexpectedly, the principal physiologic substrate for eosinophil peroxidase (EPO) and a major (i.e., accounting for 50% of H2O2 consumed) substrate for myeloperoxidase (MPO). The product of these reactions is HOSCN, a weak, exclusively sulfhydryl-reactive oxidant that we have previously shown to be a uniquely potent (up to 100-fold) oxidant transcriptional inducer of human umbilical vein endothelial cell (HUVEC) tissue factor (TF), ICAM-1 and VCAM-1 expression via a mechanism dependent upon NF-κB p65/p50 activation. We hypothesized that oxidative a

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Mcewan, P. A., Robert K. Andrews, and Jonas Emsley. "Glycoprotein Ibalpha Inhibitor Complex Crystal Structure at High Resolution." Blood 114, no. 22 (2009): 774. http://dx.doi.org/10.1182/blood.v114.22.774.774.

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Abstract Abstract 774 Introduction: The platelet Glycoprotein Ib/V/IX (GpIb/V/IX) complex is considered a major target for anticoagulant therapy. The primary function of the receptor is to mediate platelet adhesion to von Willebrand factor (VWF) bound to damaged sub-endothelium. This represents the first critical step for platelet adhesion under conditions of high fluid shear stress. GpIb/V/IX is implicated in a number of thrombotic pathological processes such as stroke or myocardial infarction and the bleeding disorders Bernard-Soulier syndrome, platelet type von Willebrand disease (Pt-VWD) a

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Sakai, Kazuya, Masataka Kuwana, Hidenori Tanaka, et al. "HLA loci predisposing to immune TTP in Japanese: potential role of the shared ADAMTS13 peptide bound to different HLA-DR." Blood 135, no. 26 (2020): 2413–19. http://dx.doi.org/10.1182/blood.2020005395.

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Abstract Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare autoimmune disorder caused by neutralizing anti-ADAMTS13 autoantibodies. In white individuals, HLA allele DRB1*11 is a predisposing factor for iTTP, whereas DRB1*04 is a protective factor. However, the role of HLA in Asians is unclear. In this study, we analyzed 10 HLA loci using next-generation sequencing in 52 Japanese patients with iTTP, and the allele frequency in the iTTP group was compared with that in a Japanese control group. We identified the following HLA alleles as predisposing factors for iTTP in the Japa

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Ahishev, D. M. "SYNTHESIS OF CALIX[4]ARENES WITH FIXED CONFORMATION AS POTENTIAL INHIBITORS OF FIBRIN POLYMERIZATION." Biotechnologia Acta 16, no. 2 (2023): 7–10. http://dx.doi.org/10.15407/biotech16.02.007.

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Aim. The purpose of the present study was to develop a method for the fixation of ‘fixed’ conformation for estimation of the impact of calix[4]arene structure on the efficacy of its anticoagulant activity. This was achieved by substitution of the lower rim of C-145 analogue. Methods.Calix[4]arene C-145F (compound 6) was obtained in 4 steps starting with Duff reaction. Calix[4]arene methylene-bis-phosphonic ester 3 was prepared via addition of diisopropylphosphite in presence of metallic sodium to the parent calix[4]arene aldehyde 2. Further steps included Mitsunobu reaction, that afforded dipr

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