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Purinergic cardiovascular

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https://www.readbyqxmd.com/read/30338362/purinergic-receptor-y-2-p2y-2-dependent-vcam-1-expression-promotes-immune-cell-infiltration-in-metabolic-syndrome
#1
Julian Merz, Philipp Albrecht, Sunaina von Garlen, Ibrahim Ahmed, Daniel Dimanski, Dennis Wolf, Ingo Hilgendorf, Carmen Härdtner, Katja Grotius, Florian Willecke, Timo Heidt, Heiko Bugger, Natalie Hoppe, Ulrich Kintscher, Constantin von Zur Mühlen, Marco Idzko, Christoph Bode, Andreas Zirlik, Peter Stachon
Sterile inflammation of visceral fat, provoked by dying adipocytes, links the metabolic syndrome to cardiovascular disease. Danger-associated molecular patterns, such as adenosine triphosphate (ATP), are released by activated or dying cells and orchestrate leukocyte infiltration and inflammation via the purinergic receptor P2Y2 . The gene expression of ATP receptor P2Y2 did not change in several tissues in the course of obesity, but was increased within epididymal fat. Adipose tissue from P2Y 2 -/- mice consuming high-fat diet (HFD) contained less crown-like structures with a reduced frequency of adipose tissue macrophages (ATMs)...
October 18, 2018: Basic Research in Cardiology
https://www.readbyqxmd.com/read/30318008/adenosine-as-a-marker-and-mediator-of-cardiovascular-homeostasis-a-translational-perspective
#2
Trevor Simard, Richard Jung, Alisha Labinaz, Mohammad Ali Faraz, F Daniel Ramirez, Pietro Di Santo, Ian Pitcher, Pouya Motazedian, Chantal Gaudet, Rebecca Rochman, Jeffrey Marbach, Paul Boland, Kiran Sarathy, Saleh Alghofaili, Juan J Russo, Etienne Couture, Robert S Beanlands, Benjamin Hibbert
Adenosine, a purine nucleoside, is produced broadly and implicated in the homeostasis of many cells and tissues. It signals predominantly via 4 purinergic adenosine receptors (ADORs) - ADORA1, ADORA2A, ADORA2B and ADORA3 in addition to non-ADOR mediated effects. Through these signaling mechanisms, adenosine exerts effects on numerous cell types crucial to maintaining vascular homeostasis, especially following vascular injury. Both in vitro and in vivo models have provided considerable insights into adenosine signaling and identified targets for therapeutic intervention...
October 10, 2018: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/30159340/the-impact-of-purinergic-system-enzymes-on-noncommunicable-neurological-and-degenerative-diseases
#3
REVIEW
Margarete Dulce Bagatini, Alessandra Antunes Dos Santos, Andréia Machado Cardoso, Aline Mânica, Cristina Ruedell Reschke, Fabiano Barbosa Carvalho
Evidences show that purinergic signaling is involved in processes associated with health and disease, including noncommunicable, neurological, and degenerative diseases. These diseases strike from children to elderly and are generally characterized by progressive deterioration of cells, eventually leading to tissue or organ degeneration. These pathological conditions can be associated with disturbance in the signaling mediated by nucleotides and nucleosides of adenine, in expression or activity of extracellular ectonucleotidases and in activation of P2X and P2Y receptors...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/30149104/myocardial-metabolism-in-heart-failure-purinergic-signalling-and-other-metabolic-concepts
#4
REVIEW
Andreas L Birkenfeld, Jens Jordan, Markus Dworak, Tobias Merkel, Geoffrey Burnstock
Despite significant therapeutic advances in heart failure (HF) therapy, the morbidity and mortality associated with this disease remains unacceptably high. The concept of metabolic dysfunction as an important underlying mechanism in HF is well established. Cardiac function is inextricably linked to metabolism, with dysregulation of cardiac metabolism pathways implicated in a range of cardiac complications, including HF. Modulation of cardiac metabolism has therefore become an attractive clinical target. Cardiac metabolism is based on the integration of adenosine triphosphate (ATP) production and utilization pathways...
August 25, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30084083/involvement-of-p2y-12-receptor-of-stellate-ganglion-in-diabetic-cardiovascular-autonomic-neuropathy
#5
Jingjing Guo, Xuan Sheng, Yu Dan, Yurong Xu, Yuanruohan Zhang, Huihong Ji, Jiayue Wang, Zixi Xu, Hongyu Che, Guodong Li, Shangdong Liang, Guilin Li
Diabetes as a chronic epidemic disease with obvious symptom of hyperglycemia is seriously affecting human health globally due to the diverse diabetic complications. Diabetic cardiovascular autonomic neuropathy (DCAN) is a common complication of both type 1 and type 2 diabetes and incurs high morbidity and mortality. However, the underlying mechanism for DCAN is unclear. It is well known that purinergic signaling is involved in the regulation of cardiovascular function. In this study, we examined whether the P2Y12 receptor could mediate DCAN-induced sympathetic reflexes...
August 6, 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29845316/adenosine-hypersensitivity-and-atrioventricular-block
#6
REVIEW
Jean-Claude Deharo, Michele Brignole, Régis Guieu
Adenosine is a ubiquitous substance that is released under several physiological and pathological conditions and has cardiovascular effects including cardioinhibition and vasodilation. It has been shown to be an important modulator implicated in several forms of syncope. In patients with chronic low plasma levels of adenosine, a transient release of endogenous adenosine can be sufficient to block conduction in the atrioventricular node and induce prolonged asystole; conversely, when plasma adenosine levels are chronically high, adenosine release is responsible for vasodepression...
June 2018: Herzschrittmachertherapie & Elektrophysiologie
https://www.readbyqxmd.com/read/29742297/advances-in-cellular-and-integrative-control-of-oxygen-homeostasis-within-the-central-nervous-system
#7
Jan Marino Ramirez, Liza J Severs, Sanja C Ramirez, Ibis M Agosto-Marlin
Mammals must continuously regulate the levels of O2 and CO2 , which is particularly important for the brain. Failure to maintain adequate O2 /CO2 homeostasis has been associated with numerous disorders including sleep apnoea, Rett syndrome and sudden infant death syndrome. But, O2 /CO2 homeostasis poses major regulatory challenges, even in the healthy brain. Neuronal activities change in a differentiated, spatially and temporally complex manner, which is reflected in equally complex changes in O2 demand. This raises important questions: is oxygen sensing an emergent property, locally generated within all active neuronal networks, and/or the property of specialized O2 -sensitive CNS regions? Increasing evidence suggests that the regulation of the brain's redox state involves properties that are intrinsic to many networks, but that specialized regions in the brainstem orchestrate the integrated control of respiratory and cardiovascular functions...
May 9, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29670001/epigenetic-programming-of-synthesis-release-and-or-receptor-expression-of-common-mediators-participating-in-the-risk-resilience-for-comorbid-stress-related-disorders-and-coronary-artery-disease
#8
REVIEW
Carlos Manuel Zapata-Martín Del Campo, Martín Martínez-Rosas, Verónica Guarner-Lans
Corticotrophin releasing factor, vasopressin, oxytocin, natriuretic hormones, angiotensin, neuregulins, some purinergic substances, and some cytokines contribute to the long-term modulation and restructuring of cardiovascular regulation networks and, at the same time, have relevance in situations of comorbid abnormal stress responses. The synthesis, release, and receptor expression of these mediators seem to be under epigenetic control since early stages of life, possibly underlying the comorbidity to coronary artery disease (CAD) and stress-related disorders (SRD)...
April 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29663535/hypothyroidism-and-hyperthyroidism-change-ectoenzyme-activity-in-rat-platelets
#9
Jucimara Baldissarelli, Adriana Santi, Roberta Schmatz, Caroline C Martins, Daniela Zanini, Karine P Reichert, Gustavo R Thomé, Taís V Palma, Pauline da Costa, Vera M Morsch, Maria R C Schetinger
The purinergic system has an important role in the regulation of vascular functions. The interference of thyroid hormones in this system and in cardiovascular events has been studied in recent years. However, the mechanisms involved in vascular, purinergic, and oxidative changes in thyroid disorders are not completely understood. Therefore, the present study aimed to assess purinergic enzyme activity in platelets from rats with hypothyroidism and hyperthyroidism induced, respectively, by continuous exposure to methimazole (MMI) at 20 mg/100 mL or L-thyroxine at 1...
July 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29470593/increased-gi-protein-signaling-potentiates-the-negative-chronotropic-effect-of-adenosine-in-the-shr-right-atrium
#10
Juliano Q D Rodrigues, Henrique Camara, Aron Jurkiewicz, Rosely O Godinho
Hypertension is a risk factor for cardiovascular diseases, which have been associated with dysfunction of sympathetic and purinergic neurotransmission. Therefore, herein, we evaluated whether modifications of adenosine receptor signaling may contribute to the cardiac dysfunction observed in hypertension. Isolated right atria from spontaneously hypertensive (SHR) or normotensive Wistar rats (NWR) were used to investigate the influence of adenosine receptor signaling cascade in the cardiac chronotropism. Our results showed that adenosine, the endogenous agonist of adenosine receptors, and CPA, a selective agonist of A1 receptor, decreased the atrial chronotropism of NWR and SHR in a concentration- and time-dependent manner, culminating in cardiac arrest (0 bpm)...
May 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29375053/expression-of-purinergic-p2x-7-receptors-in-subpopulations-of-peripheral-blood-mononuclear-cells-in-early-stage-of-chronic-kidney-disease
#11
I Lajdova, A Oksa, M Horvathova, V Spustova
Chronic kidney disease (CKD) is known as a state of chronic low-grade inflammation, enhancing cardiovascular risk and immunodeficiency. Purinergic signaling has been accepted as a crucial component in the pathogenesis of various diseases, mediating a vast array of biological processes. The P2X7 receptor is one of the important cell surface regulators of several key inflammatory molecules. The aim of the study was to examine the expression of surface P2X7 receptors in subpopulations of peripheral blood mononuclear cells (PBMCs), and to evaluate the promising prognostic markers of inflammation (neutrophil/lymphocyte, Ne/Ly ratio) and cardiovascular risk (monocyte/high density lipoprotein cholesterol, Mo/HDL ratio) in early-stage CKD...
October 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/29366837/the-p2x7-purinergic-receptor-an-emerging-therapeutic-target-in-cardiovascular-diseases
#12
REVIEW
Zhe Chen, Lu He, Lanfang Li, Linxi Chen
The P2X7 purinergic receptor, a calcium permeable cationic channel, is activated by extracellular ATP. Most studies show that P2X7 receptor plays an important role in the nervous system diseases, immune response, osteoporosis and cancer. Mounting evidence indicates that P2X7 receptor is also associated with cardiovascular disease. For example, the P2X7 receptor activated by ATP can attenuate myocardial ischemia-reperfusion injury. By contrast, inhibition of P2X7 receptor decreases arrhythmia after myocardial infarction, prolongs cardiac survival after a long term heart transplant, alleviates the dilated cardiomyopathy and the autoimmune myocarditis process...
April 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29350995/a-review-of-analytical-methods-for-the-determination-of-clopidogrel-in-pharmaceuticals-and-biological-matrices
#13
REVIEW
Kavitha J, Kokilambigai K S, Seetharaman R, Harini R R, A A Kaaviya, Sowndaravel P, Lakshmi K S
P2Y12 belongs to a group of G protein-coupled (GPCR) purinergic receptors and is a receptor for adenosine diphosphate (ADP). The P2Y12 receptor is involved in platelet aggregation and acts as a biological target for treating thromboembolisms and other clotting disorders. The use of Clopidogrel (CLO) has improved the morbidity and mortality endpoints including cardiovascular death, recurrent myocardial infarction (MI) and stroke at 30 days after percutaneous coronary intervention (PCI). CLO is one such drug that specifically and irreversibly inhibits the P2Y12 subtype of ADP receptor...
March 4, 2018: Critical Reviews in Analytical Chemistry
https://www.readbyqxmd.com/read/29346575/abacavir-induces-arterial-thrombosis-in-a-murine-model
#14
Victor Collado-Diaz, Isabel Andujar, Ainhoa Sanchez-Lopez, Samuel Orden, María Amparo Blanch-Ruiz, María Angeles Martinez-Cuesta, Ana Blas-García, Juan V Esplugues, Ángeles Álvarez
Background: The purinergic system is known to underlie prothrombotic and proinflammatory vascular programs, making the profile of experimental actions demonstrated by abacavir compatible with thrombogenesis. However, direct evidence of a prothrombotic effect by the drug has been lacking. Methods: The present study appraised the effects of abacavir in a well-validated animal model of arterial thrombosis. The role of ATP-P2X7 receptors in the actions of the drug was also assessed, and the actions of recognized vascular-damaging agents and other nucleoside reverse-transcriptase inhibitors (NRTIs) were evaluated and compared to those of abacavir...
June 20, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29322294/ticagrelor-inhibits-platelet-tumor-cell-interactions-and-metastasis-in-human-and-murine-breast-cancer
#15
Alison J Gareau, Colin Brien, Simon Gebremeskel, Robert S Liwski, Brent Johnston, Michael Bezuhly
Activated platelets promote the proliferation and metastatic potential of cancer cells. Platelet activation is largely mediated through ADP engagement of purinergic P2Y12 receptors on platelets. We examined the potential of the reversible P2Y12 inhibitor ticagrelor, an agent used clinically to prevent cardiovascular and cerebrovascular events, to reduce tumor growth and metastasis. In vitro, MCF-7, MDA-MB-468, and MDA-MB-231 human mammary carcinoma cells exhibited decreased interaction with platelets treated with ticagrelor compared to untreated platelets...
February 2018: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/29191707/changes-in-inflammatory-cardiac-markers-of-hiv-positive-patients
#16
João F P Rezer, Stephen A Adefegha, Assis Ecker, Daniela F Passos, Renata S P Saccol, Tatiana M D Bertoldo, Daniela B R Leal
HIV replication promotes atherogenesis and participates in the immune response to the virus, thereby influencing the inflammatory profile. These changes may, in turn, contribute to the risk of cardiovascular diseases with involvement of platelets. However, adenine nucleotides and nucleosides involved in thromboregulation and modulation of immune response may therefore be affected by these alterations. OBJECTIVES: This study sought to evaluate the profile of pro and anti-inflammatory cytokines (IL-10, IL-6, IL-17, TNF, IL-4, IL-2 and IFN-gamma), cardiac markers (troponin, CK, CK MB, LDH, CRP) in HIV-positive patients and assess the in vitro effect of antiretroviral therapy on the activities of ectonucleotidases (E-NTPDase and E-5'-nucleotidase) in human platelets...
January 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29155852/the-role-of-adenosine-diphosphate-mediated-platelet-responsiveness-for-the-stability-of-platelet-integrity-in-citrated-whole-blood-under-ex-vivo-conditions
#17
Juergen Koessler, Michaela Schwarz, Katja Weber, Julia Etzel, Angela Koessler, Markus Boeck, Anna Kobsar
BACKGROUND: Platelets are important for effective hemostasis and considered to be involved in pathophysiological processes, e.g. in cardiovascular diseases. Platelets provided for research or for therapeutic use are frequently separated from citrated whole blood (WB) stored for different periods of time. Although functionally intact platelets are required, the stability of platelet integrity, e.g. adenosine diphosphate (ADP) mediated responsiveness, has never been thoroughly investigated in citrated WB under ex vivo conditions...
2017: PloS One
https://www.readbyqxmd.com/read/28929376/divergent-coronary-flow-responses-to-uridine-adenosine-tetraphosphate-in-atherosclerotic-apoe-knockout-mice
#18
Bunyen Teng, Hicham Labazi, Changyan Sun, Yan Yang, Xiaorong Zeng, S Jamal Mustafa, Zhichao Zhou
Uridine adenosine tetraphosphate (Up4 A) exerts potent relaxation in porcine coronary arteries that is reduced following myocardial infarction, suggesting a crucial role for Up4 A in the regulation of coronary flow (CF) in cardiovascular disorders. We evaluated the vasoactive effects of Up4 A on CF in atherosclerosis using ApoE knockout (KO) mice ex vivo and in vivo. Functional studies were conducted in isolated mouse hearts using the Langendorff technique. Immunofluorescence was performed to assess purinergic P2X1 receptor (P2X1 R) expression in isolated mouse coronary arteries...
December 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28882235/efficacy-and-safety-of-ticagrelor-over-time-in-patients-with-prior-mi-in-pegasus-timi-54
#19
RANDOMIZED CONTROLLED TRIAL
Marc P Bonaca, Robert F Storey, Pierre Theroux, P Gabriel Steg, Deepak L Bhatt, Marc C Cohen, KyungAh Im, Sabina A Murphy, Giulia Magnani, Ton Oude Ophuis, Mikhail Rudah, Alexander Parkhomenko, Daniel Isaza, Gabriel Kamensky, Assen Goudev, Gilles Montalescot, Eva C Jensen, Per Johanson, Eugene Braunwald, Marc S Sabatine
BACKGROUND: Ticagrelor reduces ischemic risk in patients with prior myocardial infarction (MI). It remains unclear whether ischemic risk and the benefits of prolonged P2Y12 inhibition in this population remain consistent over time. OBJECTIVES: The study sought to investigate the pattern of ischemic risk over time and whether the efficacy and safety of ticagrelor were similar early and late after randomization. METHODS: The PEGASUS-TIMI (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis In Myocardial Infarction) 54 trial randomized patients with prior MI (median 1...
September 12, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28863817/regulation-of-p2x-purinergic-receptor-signaling-by-cholesterol
#20
REVIEW
Ruth D Murrell-Lagnado
P2X receptors are cation-selective channels that are activated by the binding of extracellular ATP. They have a high permeability to Ca2+ , Na+ , and K+ and are expressed widely throughout the nervous, immune, cardiovascular, skeletal, gastrointestinal, respiratory, and endocrine systems. Seven mammalian subtypes of P2X receptor subunits have been identified, P2X1-7, and those that function as homotrimeric receptors (P2X1, 2, 3, 4, and 7) are targeted to lipid rafts, although they show limited resistance to solubilization by Triton X-100...
2017: Current Topics in Membranes
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