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https://www.readbyqxmd.com/read/28079982/recombinant-soluble-apyrase-apt102-inhibits-thrombosis-and-intimal-hyperplasia-in-vein-grafts-without-adversely-affecting-hemostasis-or-re-endothelialization
#1
Y Ji, O Adeola, T L Strawn, S S Jeong, R Chen, W P Fay
BACKGROUND: Occlusion of vein grafts (VGs) after bypass surgery due to thrombosis and intimal hyperplasia (IH) is a major clinical problem. Apyrases are enzymes that scavenge extracellular ATP and ADP and promote adenosine formation at sites of vascular injury and hence have potential to inhibit vein graft pathology. OBJECTIVES: We examined the effects of recombinant soluble human apyrase, APT102, on platelets, smooth muscle cells (SMCs), and endothelial cells (ECs) in vitro and thrombosis and IH in murine VGs...
January 12, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28073290/intra-and-interorgan-communication-in-the-cardiovascular-system-a-special-view-on-redox-regulation
#2
Axel Gödecke, Judith Haendeler
Intraorgan communication in the cardiovascular system is exerted by direct cell-cell contacts, but also by locally released factors, which modulate neighboring cells by paracrine signals (e.g. NO, vascular endothelial growth factor, adenosine, reactive oxygen species (ROS)). Moreover, cells in close proximity to the typical cardiovascular cells such as fibroblasts, red blood cells, as well as resident and invading immune cells must be considered in attempts to understand cardiovascular function in physiology and pathology...
January 10, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28065166/the-predictive-capabilities-of-a-novel-cardiovascular-magnetic-resonance-derived-marker-of-cardiopulmonary-reserve-on-established-prognostic-surrogate-markers-in-patients-with-pulmonary-vascular-disease-results-of-a-longitudinal-pilot-study
#3
Timothy J Baillie, Samuel Sidharta, Peter M Steele, Stephen G Worthley, Scott Willoughby, Karen Teo, Prashanthan Sanders, Stephen J Nicholls, Matthew I Worthley
BACKGROUND: No unified method exists to effectively predict and monitor progression of pulmonary arterial hypertension (PAH). We assessed the longitudinal relationship between a novel marker of cardiopulmonary reserve and established prognostic surrogate markers in patients with pulmonary vascular disease. METHODS AND RESULTS: Twenty participants with confirmed (n = 14) or at high risk (n = 6) for PAH underwent cardiovascular magnetic resonance (CMR) at baseline and after ~6 months of guideline-appropriate management...
January 9, 2017: Journal of Cardiovascular Magnetic Resonance
https://www.readbyqxmd.com/read/28049018/transactivation-of-the-epidermal-growth-factor-receptor-in-responses-to-myocardial-stress-and-cardioprotection
#4
REVIEW
Melissa E Reichelt, Shannon O'Brien, Walter G Thomas, John P Headrick
The epidermal growth factor receptor (EGFR) family comprises the ErbB1 (EGFR) and ErbB4 receptors as well as the 'co-receptors' ErbB2 (which does not bind EGF ligands) and ErbB3 (which lack tyrosine kinase activity). This family of receptors is essential for cardiac development, myocardial, renal and vascular function, and cardiac responses to physiological and pathological perturbations. The EGFR appears critical in protecting cardiac cells from injury, while considerable attention has focussed on neuregulin/ErbB4 signalling in potentially ameliorating cardiomyopathy/heart failure...
December 31, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28038380/the-p2y2-nucleotide-receptor-is-an-inhibitor-of-vascular-calcification
#5
Shaomin Qian, Jenna N Regan, Maxwell T Shelton, April Hoggatt, Khalid S Mohammad, Paul B Herring, Cheikh I Seye
BACKGROUND AND AIMS: Mutations in the 5'-nucleotidase ecto (NT5E) gene that encodes CD73, a nucleotidase that converts AMP to adenosine, are linked to arterial calcification. However, the role of purinergic receptor signaling in the pathology of intimal calcification is not well understood. In this study, we examined whether extracellular nucleotides acting via P2Y2 receptor (P2Y2R) modulate arterial intimal calcification, a condition highly correlated with cardiovascular morbidity. METHODS: Apolipoprotein E, P2Y2R double knockout mice (ApoE(-/-)P2Y2R(-/-)) were used to determine the effect of P2Y2R deficiency on vascular calcification in vivo...
December 15, 2016: Atherosclerosis
https://www.readbyqxmd.com/read/28034895/impaired-aortic-contractility-to-uridine-adenosine-tetraphosphate-in-angiotensin-ii-induced-hypertensive-mice-receptor-desensitization
#6
Zhichao Zhou, Vishal R Yadav, Changyan Sun, Bunyen Teng, Jamal S Mustafa
OBJECTIVE: We previously showed that uridine adenosine tetraphosphate (Up4A)-mediated aortic contraction is partly mediated through purinergic P2X1 receptors (P2X1R). It has been reported that the plasma level of Up4A is elevated in hypertensive patients, implying a potential role for Up4A-P2X1R signaling in hypertension. This study investigated the vasoactive effect of Up4A in aortas isolated from angiotensin (Ang) II-infused (21 days) hypertensive mice. METHODS: Blood pressure was measured by tail cuff plethysmography...
December 29, 2016: American Journal of Hypertension
https://www.readbyqxmd.com/read/28033029/higher-platelet-reactivity-and-platelet-monocyte-complex-formation-in-gram-positive-sepsis-compared-to-gram-negative-sepsis
#7
Rahajeng N Tunjungputri, Wouter van de Heijden, Rolf T Urbanus, Philip G de Groot, Andre van der Ven, Quirijn de Mast
Platelets may play a role in the high risk for vascular complications in Gram-positive sepsis. We compared the platelet reactivity of 15 patients with Gram-positive sepsis, 17 with Gram-negative sepsis and 20 healthy controls using a whole blood flow cytometry-based assay. Patients with Gram-positive sepsis had the highest median fluorescence intensity (MFI) of the platelet membrane expression of P-selectin upon stimulation with high dose adenosine diphosphate (ADP; P = 0.002 vs. Gram-negative and P = 0.005 vs...
December 29, 2016: Platelets
https://www.readbyqxmd.com/read/28024309/stroke-as-initial-manifestation-of-adenosine-deaminase-2-deficiency
#8
Miriam Elbracht, Michael Mull, Norbert Wagner, Christiane Kuhl, Angela Abicht, Ingo Kurth, Klaus Tenbrock, Martin Häusler
Deficiency of adenosine deaminase 2 (ADA2) due to homozygous or compound heterozygous mutations in the cat eye syndrome chromosome region, candidate 1 (CECR1) gene causes an autoimmune phenotype with systemic vasculitis affecting the skin, inner organs, and the central nervous system. Typically, stroke has been reported to follow systemic inflammatory disease and predominantly affects posterior and central brain areas. Here, we describe one of the rare patients in whom acute mesencephalic stroke preceded systemic inflammation and presented as initial clinical symptom...
December 26, 2016: Neuropediatrics
https://www.readbyqxmd.com/read/28003870/new-perspective-on-maintenance-therapies-for-platinum-sensitive-recurrent-ovarian-cancer-in-women-with-germline-and-somatic-mutations-in-brca1-and-brca2-genes
#9
I Vergote, V Bours, B Blaumeiser, J-F Baurain
Ovarian cancer (OC) is the seventh most common cancer in women. Although women diagnosed with OC are usually treated frontline with platinum-based chemotherapy, most of them relapse once treatment is halted. Therefore, maintenance therapies have been developed to secure the response and delay further chemotherapy. There are two established maintenance therapies for women affected by platinum-sensitive recurrent OC: bevacizumab, a humanized monoclonal antibody targeting vascular endothelial growth factor, and olaparib, an inhibitor of poly (adenosine diphosphate [ADP]-ribose) polymerase (PARPi)...
September 2016: Facts, Views & Vision in ObGyn
https://www.readbyqxmd.com/read/27997923/the-role-of-hmgb1-in-pial-arteriole-dilating-reactivity-following-subarachnoid-hemorrhage-in-rats
#10
Haoliang Xu, Benjarat Changyaleket, Tibor Valyi-Nagy, Randal O Dull, Dale A Pelligrino, David E Schwartz, Zhao Zhong Chong
High-mobility group box 1 protein (HMGB1) has been implicated in inflammatory responses, and is also associated with cerebral vasospasm after subarachnoid hemorrhage (SAH). However, there are no direct evident links between HMGB1 and cerebral vasospasm. We therefore investigated the effects of HMGB1 on pial arteriole reactivity following SAH in rats. We initially found that SAH induced a significant decrease in pial arteriole dilating responses to sciatic nerve stimulation (SNS), hypercapnia (CO2), and the topical suffusion of acetylcholine (ACh), adenosine (ADO), and s-nitroso-N-acetylpenicillamine (SNAP) over a 7-day period after SAH...
December 21, 2016: Journal of Vascular Research
https://www.readbyqxmd.com/read/27997894/zedoarondiol-inhibits-platelet-derived-growth-factor-induced-vascular-smooth-muscle-cells-proliferation-via-regulating-amp-activated-protein-kinase-signaling-pathway
#11
Huimin Mao, Tianqi Tao, Dandan Song, Mi Liu, Xiaoren Wang, Xiuhua Liu, Dazhuo Shi
BACKGROUND/AIMS: Vascular smooth muscle cells (VSMCs) proliferation contributes significantly to atherosclerosis and in-stent restenosis. Platelet-derived growth factor-BB (PDGF-BB) plays a vital role in VSMCs proliferation. Zedoarondiol, a sesquiterpene lactone compound, has an anti-inflammatory activity. However, the role of zedoarondiol in PDGF-BB-mediated VSMCs proliferation remains unclear. In this study, we investigated the effects of zedoarondiol on PDGF-BB-induced VSMCs proliferation and explored the possible mechanisms...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27965423/increased-activity-of-tnap-compensates-for-reduced-adenosine-production-and-promotes-ectopic-calcification-in-the-genetic-disease-acdc
#12
Hui Jin, Cynthia St Hilaire, Yuting Huang, Dan Yang, Natalia I Dmitrieva, Alejandra Negro, Robin Schwartzbeck, Yangtengyu Liu, Zhen Yu, Avram Walts, Jean-Michel Davaine, Duck-Yeon Lee, Danielle Donahue, Kevin S Hsu, Jessica Chen, Tao Cheng, William Gahl, Guibin Chen, Manfred Boehm
ACDC (arterial calcification due to deficiency of CD73) is an autosomal recessive disease resulting from loss-of-function mutations in NT5E, which encodes CD73, a 5'-ectonucleotidase that converts extracellular adenosine monophosphate to adenosine. ACDC patients display progressive calcification of lower extremity arteries, causing limb ischemia. Tissue-nonspecific alkaline phosphatase (TNAP), which converts pyrophosphate (PPi) to inorganic phosphate (Pi), and extracellular purine metabolism play important roles in other inherited forms of vascular calcification...
December 13, 2016: Science Signaling
https://www.readbyqxmd.com/read/27941054/tetrahydrobiopterin-rescues-impaired-responses-of-cerebral-resistance-arterioles-during-type-1-diabetes
#13
William G Mayhan, Denise M Arrick
Our goal was to test the hypothesis that administration of tetrahydrobiopterin (BH4) would improve impaired endothelial nitric oxide synthase-dependent dilation of cerebral arterioles during type 1 diabetes. In addition, we examined the influence of BH4 on levels of superoxide in brain tissue. In vivo diameter of cerebral arterioles in nondiabetic and diabetic rats was measured in response to endothelial nitric oxide synthase-dependent agonists (acetylcholine and adenosine 5'-diphosphate) and an endothelial nitric oxide synthase-independent agonist (nitroglycerine) before and during application of BH4 (1...
January 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/27938345/assessment-of-platelet-function-in-patients-with-stroke-using-multiple-electrode-platelet-aggregometry-a-prospective-observational-study
#14
Ahmed Sabra, Sophia N Stanford, Sharon Storton, Matthew Lawrence, Lindsay D'Silva, Roger H K Morris, Vanessa Evans, Mushtaq Wani, John F Potter, Phillip A Evans
BACKGROUND: There is a link between high on-treatment platelet reactivity (HPR) and adverse vascular events in stroke. This study aimed to compare multiple electrode platelet aggregometry (MEA), in healthy subjects and ischaemic stroke patients, and between patients naive to antiplatelet drugs (AP) and those on regular low dose AP. We also aimed to determine prevalence of HPR at baseline and at 3-5 days after loading doses of aspirin. METHODS: Patients with first ever ischaemic stroke were age and sex-matched to a healthy control group...
December 9, 2016: BMC Neurology
https://www.readbyqxmd.com/read/27919027/phosphorylation-of-janus-kinase-1-jak1-by-amp-activated-protein-kinase-ampk-links-energy-sensing-to-anti-inflammatory-signaling
#15
Claire Rutherford, Claire Speirs, Jamie J L Williams, Marie-Ann Ewart, Sarah J Mancini, Simon A Hawley, Christian Delles, Benoit Viollet, Ana P Costa-Pereira, George S Baillie, Ian P Salt, Timothy M Palmer
Adenosine 5'-monophosphate-activated protein kinase (AMPK) is a pivotal regulator of metabolism at cellular and organismal levels. AMPK also suppresses inflammation. We found that pharmacological activation of AMPK rapidly inhibited the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway in various cells. In vitro kinase assays revealed that AMPK directly phosphorylated two residues (Ser(515) and Ser(518)) within the Src homology 2 domain of JAK1. Activation of AMPK enhanced the interaction between JAK1 and 14-3-3 proteins in cultured vascular endothelial cells and fibroblasts, an effect that required the presence of Ser(515) and Ser(518) and was abolished in cells lacking AMPK catalytic subunits...
November 8, 2016: Science Signaling
https://www.readbyqxmd.com/read/27908642/negative-regulation-of-nlrp3-inflammasome-by-sirt1-in-vascular-endothelial-cells
#16
Yanxiang Li, Xiaofeng Yang, Yanhao He, Weirong Wang, Jiye Zhang, Wei Zhang, Ting Jing, Bo Wang, Rong Lin
NLRP3 inflammasome not only functions as a critical effector in innate immunity, but also triggers the production of proinflammatory cytokines involved in inflammation-associated diseases. Sirtuin 1 (SIRT1) plays an important role in the regulation of cellular inflammation. However, whether the activation of NLRP3 inflammasome is regulated by SIRT1 remains unknown. In this study, we investigated the regulatory effect of SIRT1 on NLRP3 inflammasome and the underlying mechanisms. We found that lipopolysaccharide (LPS) and adenosine triphosphate (ATP)-induced the activation of NLRP3 inflammasome in human umbilical vein endothelial cells (HUVECs)...
November 4, 2016: Immunobiology
https://www.readbyqxmd.com/read/27906619/effects-of-4-pyridone-3-carboxamide-1%C3%AE-d-ribonucleoside-on-adenine-nucleotide-catabolism-in-the-aortic-wall-implications-for-atherosclerosis-in-apoe-ldlr-mice
#17
Magdalena Zabielska, Barbara Kutryb-Zajac, Paulina Żukowska, Ewa Slominska, Ryszard Smoleński
: 4-Pyridone-3-carboxamide-1-beta-D-ribonucleoside (4PYR) is an endogenously produced nucleoside that had been identified as a substrate for intracellular phosphorylation to form intracellular nucleotides. Previous studies demonstrated that 4PYR adversely affects metabolism of endothelial cells that is known risk factor for atherosclerosis. The purpose of this study was to evaluate effects of 4PYR on the progression of atherosclerosis and changes in extracellular nucleotides degradation on the surface of the vessel wall in the murine model...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27881059/natural-products-with-antiplatelet-action
#18
Gabriela Elisa Hirsch, Paulo Ricardo Nazário Viecili, Amanda Spring de Almeida, Sabrina Nascimento, Fernando Garcez Porto, Juliana Otero, Aline Schmidt, Brenda da Silva, Mariana Migliorini Parisi, Jonatas Zeni Klafke
BACKGROUND: Complex hemostatic mechanisms are involved in the pathophysiology of various diseases, including cardiovascular diseases. Among them, dysregulation of platelet activity is linked to the progression of atherosclerosis and mainly involves platelet aggregation and a decrease in blood flow in the vascular endothelium. The major platelet activation pathways mediated by agonists involve the arachidonic acid pathway, adenosine diphosphate pathway, serotonin pathway, nitric oxide pathway, and action of free radicals on molecules involved in platelet aggregation...
November 23, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27871900/insulin-adenosine-axis-linked-signalling
#19
REVIEW
Luis Silva, Mario Subiabre, Joaquín Araos, Tamara Sáez, Rocío Salsoso, Fabián Pardo, Andrea Leiva, Rody San Martín, Fernando Toledo, Luis Sobrevia
Regulation of blood flow depends on systemic and local release of vasoactive molecules such as insulin and adenosine. These molecules cause vasodilation by activation of plasma membrane receptors at the vascular endothelium. Adenosine activates at least four subtypes of adenosine receptors (A1AR, A2AAR, A2BAR, A3AR), of which A2AAR and A2BAR activation leads to increased cAMP level, generation of nitric oxide, and relaxation of the underlying smooth muscle cell layer. Vasodilation caused by adenosine also depends on plasma membrane hyperpolarization due to either activation of intermediate-conductance Ca(2+)-activated K(+) channels in vascular smooth muscle or activation of ATP-activated K(+) channels in the endothelium...
November 19, 2016: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/27856430/glycolysis-and-oxidative-phosphorylation-are-essential-for-purinergic-receptor-mediated-angiogenic-responses-in-vasa-vasorum-endothelial-cells
#20
Martin Lapel, Philip Weston, Derek Strassheim, Vijaya Karoor, Nana Burns, Taras Lyubchenko, Petr Paucek, Kurt R Stenmark, Evgenia V Gerasimovskaya
Angiogenesis is an energy-demanding process; however, the role of cellular energy pathways and their regulation by extracellular stimuli, especially extracellular nucleotides, remain largely unexplored. Using metabolic inhibitors of glycolysis (2-deoxyglucose) and oxidative phosphorylation (OXPHOS) (oligomycin, rotenone, and FCCP), we demonstrate that glycolysis and OXPHOS are both essential for angiogenic responses of vasa vasorum endothelial cell (VVEC). Treatment with P2R agonists, ATP, and 2-methylthioadenosine diphosphate trisodium salt (MeSADP), but not P1 receptor agonist, adenosine, increased glycolytic activity in VVEC (measured by extracellular acidification rate and lactate production)...
January 1, 2017: American Journal of Physiology. Cell Physiology
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