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A Novel Role for the AnxA1-Fpr2/ALX Signaling Axis as a Key Regulator of Platelet Function to Promote Resolution of Inflammation.
Conclusions: AnxA1 affords protection by altering the platelet phenotype in cerebral I/RI from pro-pathogenic to regulatory, and reducing the propensity for platelets to aggregate and cause thrombosis by affecting integrin (αIIbβ3) activation, a previously unknown phenomenon. Thus, our data reveal a novel multi-faceted role for AnxA1 to act both as a therapeutic and a prophylactic drug via its ability to promote endogenous pro-resolving, anti-thrombo-inflammatory circuits in cerebral I/RI. Collectively, these results further advance our knowledge and understanding in the field of platelet and Resolution Biology. PMI...
Source: Circulation - June 2, 2019 Category: Cardiology Authors: Senchenkova EY, Ansari J, Becker F, Vital SA, Al-Yafeai Z, Sparkenbaugh EM, Pawlinski R, Stokes KY, Carroll JL, Dragoi AM, Qin CX, Ritchie RH, Sun H, Cuellar-Saenz HH, Rubinstein MR, Han YW, Orr AW, Perretti M, Granger DN, Gavins FNE Tags: Circulation Source Type: research

TMEM16F Aggravates Neuronal Loss by Mediating Microglial Phagocytosis of Neurons in a Rat Experimental Cerebral Ischemia and Reperfusion Model
In this study, a middle-cerebral-artery occlusion/reperfusion (MCAO/R) model was used in adult male Sprague-Dawley rats in vivo, and cultured neurons were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) to simulate cerebral ischemia-reperfusion (I/R) injury in vitro. We found that the protein level of TMEM16F was significantly increased at 12 h after I-R injury both in vivo and in vitro, and reversible phosphatidylserine exposure was confirmed in neurons undergoing I/R injury in vitro. Additionally, we constructed a LV-TMEM16F-RNAi transfection system to suppress the expression of TMEM16F during and after cereb...
Source: Frontiers in Immunology - July 6, 2020 Category: Allergy & Immunology Source Type: research

Calcified amorphous tumor of the heart with mitral annular calcification: a case report
ConclusionsIn the present case, a calcified amorphous tumor arose from mitral annular calcification. A characteristic of mitral annular calcification-related calcified amorphous tumor is its highly mobile nature, with a high risk of stroke or other systemic embolism. Therefore, surgical therapy should be considered for treatment of calcified amorphous tumors.
Source: Journal of Medical Case Reports - July 18, 2017 Category: General Medicine Source Type: research

Novel endogenous negative modulators of platelet function as potential anti-thrombotic targets.
Authors: Li YJ, Zhu HX, Zhang D, Li HC, Ma P, Huang LY Abstract Platelets are megakaryocyte-derived nuclear-free fragments that participate in cardiovascular diseases including acute myocardial infarction, ischemic stroke, hypertension, and atherosclerosis. At the endothelium damage site, platelets interact with sub-endothelial matrix proteins such as glycoprotein VI/Fc receptor γ-chain (GPVI/FcRγ), G protein-coupled receptor/phospholipase Cγ(β) (GPCR/PLCγ(β)), Rho/RhoK and integrin. The activation of these signaling pathways triggers intracellular calcium increase and causes platelet adhesion, aggregation, g...
Source: European Review for Medical and Pharmacological Sciences - July 27, 2017 Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research

CK2{beta} regulates thrombopoiesis and Ca2+-triggered platelet activation in arterial thrombosis
Platelets, anucleated megakaryocyte (MK)-derived cells, play a major role in hemostasis and arterial thrombosis. Although protein kinase casein kinase 2 (CK2) is readily detected in MKs and platelets, the impact of CK2-dependent signaling on MK/platelet (patho-)physiology has remained elusive. The present study explored the impact of the CK2 regulatory β-subunit on platelet biogenesis and activation. MK/platelet-specific genetic deletion of CK2β (ck2β–/–) in mice resulted in a significant macrothrombocytopenia and an increased extramedullar megakaryopoiesis with an enhanced proportion of prematur...
Source: Blood - December 21, 2017 Category: Hematology Authors: Münzer, P., Walker-Allgaier, B., Geue, S., Langhauser, F., Geuss, E., Stegner, D., Aurbach, K., Semeniak, D., Chatterjee, M., Gonzalez Menendez, I., Märklin, M., Quintanilla-Martinez, L., Salih, H. R., Litchfield, D. W., Buchou, T., Kleins Tags: Platelets and Thrombopoiesis, Thrombosis and Hemostasis Source Type: research

Aortic Root Calcification Score as an Independent Factor for Predicting Major Adverse Cardiac Events in Familial Hypercholesterolemia.
CONCLUSIONS: ARC was significantly associated with future MACE in Japanese patients with heterozygous FH. ARC may start to develop, on average, at 17.4 and 19.7 years of age in males and females, respectively, with heterozygous FH. PMID: 29321389 [PubMed - as supplied by publisher]
Source: Journal of Atherosclerosis and Thrombosis - January 14, 2018 Category: Cardiology Tags: J Atheroscler Thromb Source Type: research

Aggregation is impaired in starved platelets due to enhanced autophagy and cellular energy depletion.
Authors: Paul M, Hemshekhar M, Kemparaju K, Girish KS Abstract Platelet hyperactivity is the hallmark of thrombosis and hemostasis disorders including atherosclerosis, diabetes, stroke, arthritis, and cancer causing significant mortality and morbidity. Therefore, regulating platelet hyperactivity is an ever growing interest. Very recently, basal autophagic process has been demonstrated to be essential for normal functioning of platelets. However, autophagy can be elevated above basal level under conditions like starvation, and how platelets respond in these settings remains to be elucidative. Therefore, in this stu...
Source: Platelets - May 30, 2018 Category: Hematology Tags: Platelets Source Type: research

Gintonin modulates platelet function and inhibits thrombus formation via impaired glycoprotein VI signaling.
In this study, we explored the anti-platelet activity of gintonin (a recently discovered non-saponin fraction of ginseng) against agonist-induced platelet activation. In vitro effects of gintonin on agonist-induced human and rat platelet aggregation, granule secretion, integrin αIIbβ3 activation, and intracellular calcium ion ([Ca2+]i) mobilization were examined. Western blot analysis and immunoprecipitation techniques were used to estimate the expression of mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and interaction of glycoprotein VI (GPVI) signaling pathway...
Source: Platelets - June 6, 2018 Category: Hematology Tags: Platelets Source Type: research

Platelet Signaling in Primary Haemostasis and Arterial Thrombus Formation: Part 1.
Abstract Platelets react immediately in response to traumatic vascular injury by adhesion, activation, aggregation and subsequent haemostatic plug formation. While this reaction pattern is essential for haemostasis, platelet responses can also cause occlusive thrombi in diseased arteries, leading to myocardial infarction or stroke. Initially, flowing platelets are captured from the circulation to vascular lesions. This step is mediated by glycoprotein (GP) Ib-IX-V interacting with immobilized von Willebrand factor (VWF) on exposed subendothelial components. Tethered platelets can now bind to collagen through GPVI ...
Source: Hamostaseologie - October 23, 2018 Category: Hematology Authors: Scharf RE Tags: Hamostaseologie Source Type: research

Assessment of Non-vitamin K Oral Anticoagulants Use in a Tertiary Care Center in the USA: A Chart Review of 909 Patients
ConclusionA significant number of patients received NOACs at doses inconsistent with the package labeling or had clinically significant drug –drug interactions with NOACs. Efforts are warranted to improve appropriate dosing and avoid significant drug interactions.
Source: American Journal of Cardiovascular Drugs - November 8, 2018 Category: Cardiology Source Type: research

Determination of the Structural Changes Accompanying Binding of Protein S to Factor IXa
Conclusion: Based on our preliminary data, we conclude that PS binds strongly with FIXa, and the complex is stabilized by a shift in α-helical content as shown in Figure 1.Figure.1 shows the CD spectral change of PS (curve 1, right panel) due to addition of different concentration of FIXa (curve 2-8, right panel).DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Chatterjee, S., Guidry, J. J., Plautz, W. E., Watt, T., Majumder, R. Tags: 321. Blood Coagulation and Fibrinolytic Factors: Structural Biology of Coagulation Proteins Source Type: research

Regulatory Genetic Variation at the S100B Gene Associates with Vaso-Occlusive Manifestations in Sickle Cell Disease
In sickle cell disease (SCD) polymerization of hemoglobin S under deoxygenated conditions causes vaso-occlusion, which can manifest as acute pain crisis and progressive bone/organ damage. Molecular studies have attributed vaso-occlusion to elevated vascular adhesion and inflammatory responses, whereas the genetic regulation has only recently been assessed.Genomic DNA isolated from peripheral blood mononuclear cells (PBMCs) was hybridized to Illumina Human 610-Quad SNP array for the PUSH and Walk-PHaSST cohorts and to Affrymetrix SNP 6.0 array for the Howard SCD expression cohort. Single nucleotide polymorphisms (SNPs) for ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Zhang, X., Zhang, W., Saraf, S. L., Nekhai, S., Gladwin, M. T., Machado, R., Gordeuk, V. R. Tags: 113. Hemoglobinopathies, Excluding Thalassemia-Basic and Translational Science: Poster I Source Type: research

The role of calcium handling mechanisms in reperfusion injury.
Abstract Cardiovascular diseases, such as stroke and myocardial infarction (MI) remain the major cause of death and disability worldwide. However, the mortality of MI has declined dramatically over the past several decades because of advances in medicines (thrombolytic agents, antiplatelet drugs, beta blockers, and angiotensin converting enzyme inhibitors) and approaches to restore tissue perfusion(percutaneous coronary intervention and cardiopulmonary bypass). Animals studies have been shown that these treatments have been effective in reducing acute myocardial ischemic injury and limiting MI size. The paradox is...
Source: Current Pharmaceutical Design - November 20, 2018 Category: Drugs & Pharmacology Authors: Pittas K, Vrachatis DA, Angelidis C, Tsoucala S, Giannopoulos G, Defteros S Tags: Curr Pharm Des Source Type: research

An assay to measure levels of factor Xa inhibitors in blood and plasma.
CONCLUSION: The assay is ideal for rapidly and accurately measuring DOAC levels in plasma and blood, demonstrating its potential for point-of-care applications. This article is protected by copyright. All rights reserved. PMID: 30985986 [PubMed - as supplied by publisher]
Source: Thrombosis and Haemostasis - April 14, 2019 Category: Hematology Authors: Kim PY, Di Giuseppantonio LR, Wu C, Douketis JD, Gross PL Tags: J Thromb Haemost Source Type: research

Force Sensing by Piezo Channels in Cardiovascular Health and Disease.
Abstract Mechanical forces are fundamental in cardiovascular biology, and deciphering the mechanisms by which they act remains a testing frontier in cardiovascular research. Here, we raise awareness of 2 recently discovered proteins, Piezo1 and Piezo2, which assemble as transmembrane triskelions to combine exquisite force sensing with regulated calcium influx. There is emerging evidence for their importance in endothelial shear stress sensing and secretion, NO generation, vascular tone, angiogenesis, atherosclerosis, vascular permeability and remodeling, blood pressure regulation, insulin sensitivity, exercise per...
Source: Arteriosclerosis, Thrombosis and Vascular Biology - September 18, 2019 Category: Cardiology Authors: Beech DJ, Kalli AC Tags: Arterioscler Thromb Vasc Biol Source Type: research

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