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https://www.readbyqxmd.com/read/28139223/urinary-11-dehydro-thromboxane-b2-and-mortality-in-patients-with-stable-coronary-artery-disease
#1
Peter A McCullough, Anupama Vasudevan, Mohanakrishnan Sathyamoorthy, Jeffrey M Schussler, Carlos E Velasco, Luis R Lopez, Caren Swift, Margarita Peterson, Jenna Bennett-Firmin, Raphael Schiffmann, Teodoro Bottiglieri
Antiplatelet therapy with aspirin has been shown to reduce adverse outcomes in patients with coronary artery disease (CAD). Aspirin irreversibly inhibits platelet cyclooxygenase-1 and attenuates thromboxane A2 (TXA2)-mediated platelet aggregation, but there is variable suppression of cyclooxygenase-1. From a cohort of patients with stable CAD, we performed blinded, detailed chart abstraction, and measured urinary 11-dehydro-thromboxane B2 (11dhTxB2), an inactive metabolite of TxA2 from frozen samples. There were 327 men (73%) and 122 women (27%) with a mean age (±SD) of 67 ± 10 and 65 ± 10 years, respectively...
January 5, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28123708/synthetic-polyphosphate-inhibits-endogenous-coagulation-and-platelet-aggregation-in-vitro
#2
Xiaoyang Yang, Mengjie Wan, Ting Liang, Minyuan Peng, Fangping Chen
Platelet-derived polyphosphate has previously been indicated to induce coagulation. However, industrially synthesized polyphosphate has been found to have different effects from those of the platelet-derived form. The present study investigated whether synthetic sodium polyphosphate inhibits coagulation using routine coagulation tests and thromboelastography. Synthetic polyphosphate was found to inhibit adenosine diphosphate-, epinephrine-, arachidonic acid-, ristocetin-, thrombin-, oxytocin- and pituitrin-induced platelet aggregation...
January 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28115138/endocannabinoid-2-arachidonoylglycerol-protects-inflammatory-insults-from-sulfur-dioxide-inhalation-via-cannabinoid-receptors-in-the-brain
#3
Ben Li, Minjun Chen, Lin Guo, Yang Yun, Guangke Li, Nan Sang
Sulfur dioxide (SO2) pollution in the atmospheric environment causes brain inflammatory insult and inflammatory-related microvasculature dysfunction. However, there are currently no effective medications targeting the harmful outcomes from chemical inhalation. Endocannabinoids (eCBs) are involved in neuronal protection against inflammation-induced neuronal injury. The 2-arachidonoylglycerol (2-AG), the most abundant eCBs and a full agonist for cannabinoid receptors (CB1 and CB2), is also capable of suppressing proinflammatory stimuli and improving microvasculature dysfunction...
January 2017: Journal of Environmental Sciences (China)
https://www.readbyqxmd.com/read/28108419/regulation-of-protein-kinase-c-related-kinase-prk-signalling-by-the-tp%C3%AE-and-tp%C3%AE-isoforms-of-the-human-thromboxane-a2-receptor-implications-for-thromboxane-and-androgen-dependent-neoplastic-and-epigenetic-responses-in-prostate-cancer
#4
Aine G O'Sullivan, Eamon P Mulvaney, B Therese Kinsella
The prostanoid thromboxane (TX) A2 and its T Prostanoid receptor (the TP) are increasingly implicated in prostate cancer (PCa). Mechanistically, we recently discovered that both TPα and TPβ form functional signalling complexes with members of the protein kinase C-related kinase (PRK) family, AGC- kinases essential for the epigenetic regulation of androgen receptor (AR)-dependent transcription and promising therapeutic targets for treatment of castrate-resistant prostate cancer (CRPC). Critically, similar to androgens, activation of the PRKs through the TXA2/TP signalling axis induces phosphorylation of histone H3 at Thr11 (H3Thr11), a marker of androgen-induced chromatin remodelling and transcriptional activation, raising the possibility that TXA2-TP signalling can mimic and/or enhance AR-induced cellular changes even in the absence of circulating androgens such as in CRPC...
January 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28069828/lpa1-receptor-mediated-thromboxane-a2-release-is-responsible-for-lysophosphatidic-acid-induced-vascular-smooth-muscle-contraction
#5
Péter Tibor Dancs, Éva Ruisanchez, Andrea Balogh, Cecília Rita Panta, Zsuzsanna Miklós, Rolf M Nüsing, Junken Aoki, Jerold Chun, Stefan Offermanns, Gábor Tigyi, Zoltán Benyó
Lysophosphatidic acid (LPA) has been recognized recently as an endothelium-dependent vasodilator, but several lines of evidence indicate that it may also stimulate vascular smooth muscle cells (VSMCs), thereby contributing to vasoregulation and remodeling. In the present study, mRNA expression of all 6 LPA receptor genes was detected in murine aortic VSMCs, with the highest levels of LPA1, LPA2, LPA4, and LPA6 In endothelium-denuded thoracic aorta (TA) and abdominal aorta (AA) segments, 1-oleoyl-LPA and the LPA1-3 agonist VPC31143 induced dose-dependent vasoconstriction...
January 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28031017/nitric-oxide-signaling-and-the-cross-talk-with-prostanoids-pathways-in-vascular-system
#6
Bruno R Silva, Tiago D Paula, Michele Paulo, Lusiane M Bendhack
BACKGROUND: This review provides an overview of the cellular signaling of nitric oxide (NO) and prostanoids in vascular cells and the possible cross talk between their pathways, mainly in hypertension, since the imbalance of these two systems has been attributed to development of some cardiovascular diseases. It also deals with the modulation of vasodilation induced by NO donors. NO is a well-known second messenger involved in many cellular functions. CONCLUSION: In the vascular system, the NO produced by endothelial NO-synthase (eNOS) or released by NO donors acts in vascular smooth muscle cells, the binding of NO to Fe2+-heme of soluble guanylyl-cyclase (sGC) activates sGC and the production of cyclic guanosine-3-5-monophosphate (cGMP)...
December 28, 2016: Medicinal Chemistry
https://www.readbyqxmd.com/read/28028021/ask1-regulates-platelet-granule-secretion-thromboxane-a2-generation-and-thrombus-formation-in-mice
#7
Meghna U Naik, Pravin Patel, Randall Derstine, Ramya Turaga, Xi Chen, Kalyan Golla, Keith B Neeves, Hidenori Ichijo, Ulhas P Naik
Mitogen activated protein kinases (MAPKs) are expressed in platelets and are activated downstream of physiological agonists. Pharmacological and genetic evidence indicate that MAPKs play a significant role in hemostasis and thrombosis, but it is not well understood how MAPKs are activated upon platelet stimulation. Here, we show that Apoptosis Signal-regulating Kinase 1 (ASK1), a member of the MAP3K family, is expressed in both human and murine platelets. ASK1 is rapidly and robustly activated upon platelet stimulation by physiological agonists...
December 27, 2016: Blood
https://www.readbyqxmd.com/read/27951728/effects-of-astaxanthin-on-blood-coagulation-fibrinolysis-and-platelet-aggregation-in-hyperlipidemic-rats
#8
Zu-Yue Deng, Wei-Guang Shan, Shen-Feng Wang, Meng-Mei Hu, Yan Chen
CONTEXT: Astaxanthin (ASTX) is a xanthophyll carotenoid that reduces hemostasis in hyperlipidemic organisms. Its antihemostatic mechanisms remain unclear. OBJECTIVE: The effects of ASTX on coagulation, the fibrinolytic system and platelet aggregation were investigated in hyperlipidemic rats. MATERIALS AND METHODS: Different doses of ASTX (5, 10 and 30 mg/kg/day, p.o.) were administered for four weeks to high-fat diet-induced hyperlipidemic rats...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/27934923/timosaponin-aiii-induces-antiplatelet-and-antithrombotic-activity-via-gq-mediated-signaling-by-the-thromboxane-a2-receptor
#9
Yue Cong, Limei Wang, Renjun Peng, Yang Zhao, Fan Bai, Chao Yang, Xiaolan Liu, Daqian Wang, Baiping Ma, Yuwen Cong
The thromboxane (Tx) A2 pathway is a major contributor to the amplification of initial platelet activation and is therefore a key drug target. To identify potent small-molecule inhibitors of the thromboxane prostaglandin (TP) receptor, we screened a small steroidal saponin library using U46619-induced rat platelet aggregation assays. Timosaponin AIII (TAIII) was identified as a potent inhibitor of U46619-induced rat platelet aggregation and exhibited superior selectivity for the TP receptor versus other G protein-coupled receptors and a PKC activator...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27927214/antiplatelet-and-antithrombotic-effects-of-cordycepin-enriched-wib-801ce-from-cordyceps-militaris-ex-vivo-in-vivo-and-in-vitro
#10
Hyuk-Woo Kwon, Jung-Hae Shin, Deok Hwi Lim, Woo Jeong Ok, Gi Suk Nam, Min Ji Kim, Ho-Kyun Kwon, Jun-Hee Noh, Je-Young Lee, Hyun-Hong Kim, Jong-Lae Kim, Hwa-Jin Park
BACKGROUND: A species of the fungal genus Cordyceps has been used as a complementary and alternative medicine of traditional Chinese medicine, and its major component cordycepin and cordycepin-enriched WIB-801CE are known to have antiplatelet effects in vitro. However, it is unknown whether they have also endogenous antiplatelet and antithrombotic effects. In this study, to resolve these doubts, we prepared cordycepin-enriched WIB-801CE, an ethanol extract from Cordyceps militaris-hypha, then evaluated its ex vivo, in vivo, and in vitro antiplatelet and antithrombotic effects...
December 7, 2016: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27893755/quantification-of-arachidonic-acid-and-its-metabolites-in-rat-tissues-by-uhplc-ms-ms-application-for-the-identification-of-potential-biomarkers-of-benign-prostatic-hyperplasia
#11
Qiaoxia Bian, Weihui Wang, Nannan Wang, Yan Peng, Wen Ma, Ronghua Dai
To evaluate the potential relationship between benign prostatic hyperplasia (BPH) and the arachidonic acid (AA) metabolome, a UHPLC-MS/MS method has been developed and validated for simultaneous determination of AA and its cyclooxygenase(COX) and lipoxygenase(LOX) pathway metabolites (15-HETE, 12-HETE, TXA2, 5-HETE, AA, PGI2, PGF2α, 8-HETE, PGD2, PGE2 and LTB4) in rat tissues. The analytes were extracted from tissue samples with a protein precipitation procedure and then separated on a Shim-pack XR-ODSC18 column with 0...
2016: PloS One
https://www.readbyqxmd.com/read/27852128/antagonistic-effects-of-gingko-biloba-and-sophora-japonica-on-cerebral-vasoconstriction-in-response-to-histamine-5-hydroxytryptamine-u46619-and-bradykinin
#12
Ha Thi Thanh Nguyen, Hai Thanh Nguyen, Md Zahorul Islam, Takeshi Obi, Pitchaya Pothinuch, Thanh Van Nguyen, Tuong Manh Nguyen, Cuong Van Dao, Mitsuya Shiraishi, Atsushi Miyamoto
The aim of this study was to evaluate, for the first time, the antagonistic effects of Gingko biloba leaf (GB) and Sophora japonica L. flower bud (SJ) extracts on cerebral vasoconstriction in response to KCl, extracellular Ca[Formula: see text], histamine, 5-hydroxytryptamine (5-HT), 9,11-dideoxy-9[Formula: see text],11[Formula: see text]-methanoepoxy prostaglandin (PG) F[Formula: see text](U46619) and bradykinin (BK), in order to explain their traditional application for diseases associated with cerebral vasospasm...
2016: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/27845343/directed-transport-of-neutrophil-derived-extracellular-vesicles-enables-platelet-mediated-innate-immune-response
#13
Jan Rossaint, Katharina Kühne, Jennifer Skupski, Hugo Van Aken, Mark R Looney, Andres Hidalgo, Alexander Zarbock
The innate immune response to bacterial infections requires the interaction of neutrophils and platelets. Here, we show that a multistep reciprocal crosstalk exists between these two cell types, ultimately facilitating neutrophil influx into the lung to eliminate infections. Activated platelets adhere to intravascular neutrophils through P-selectin/P-selectin glycoprotein ligand-1 (PSGL-1)-mediated binding, a primary interaction that allows platelets glycoprotein Ibα (GPIbα)-induced generation of neutrophil-derived extracellular vesicles (EV)...
November 15, 2016: Nature Communications
https://www.readbyqxmd.com/read/27826703/leukotriene-receptor-antagonists-and-antiallergy-drugs
#14
Tsutomu Tamada, Masakazu Ichinose
As one of the candidates of the therapeutic strategy for asthma in addition to inhaled corticosteroids (ICS), leukotriene receptor antagonists (LTRAs) are known to be useful for long-term management of asthma patients complicated by allergic rhinitis (AR) or exercise-induced asthma (EIA). Currently available LTRAs are pranlukast hydrate, zafirlukast, and montelukast. These LTRAs have a bronchodilator action and inhibit airway inflammation, resulting in a significant improvement of asthma symptoms, respiratory function, inhalation frequency of as-needed inhaled β2-agonist, airway inflammation, airway hyperresponsiveness, dosage of ICSs, asthma exacerbations, and patients' QOL...
November 9, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27695417/antiplatelet-agents-inhibit-the-generation-of-platelet-derived-microparticles
#15
Alice Giacomazzi, Maurizio Degan, Stefano Calabria, Alessandra Meneguzzi, Pietro Minuz
Platelet microparticles (PMPs) contribute to thrombogenesis but the effects of antiplatelet drugs on PMPs generation is undefined. The present study investigated the cellular events regulating PMPs shedding, testing in vitro platelet agonists and inhibitors. Platelet-rich plasma from healthy subjects was stimulated with arachidonic acid (AA), U46619, collagen type-I (10 and 1.5 μg/mL), epinephrine, ADP or TRAP-6 and pre-incubated with acetylsalicylic acid (ASA, 100 and 10 μmol/L), SQ-29,548, apyrase, PSB-0739, or eptifibatide...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27689401/expression-of-the-tp%C3%AE-and-tp%C3%AE-isoforms-of-the-thromboxane-prostanoid-receptor-tp-in-prostate-cancer-clinical-significance-and-diagnostic-potential
#16
Eamon P Mulvaney, Christine Shilling, Sarah B Eivers, Antoinette S Perry, Anders Bjartell, Elaine W Kay, R William Watson, B Therese Kinsella
The prostanoid thromboxane (TX)A2 plays a central role in haemostasis and is increasingly implicated in cancer progression. TXA2 signals through two T Prostanoid receptor (TP) isoforms termed TPα and TPβ, with both encoded by the TBXA2R gene. Despite exhibiting several functional and regulatory differences, the role of the individual TP isoforms in neoplastic diseases is largely unknown.This study evaluated expression of the TPα and TPβ isoforms in tumour microarrays of the benign prostate and different pathological (Gleason) grades of prostate cancer (PCa)...
8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27688244/endometriosis-derived-thromboxane-a2-induces-neurite-outgrowth
#17
Dingmin Yan, Xishi Liu, Sun-Wei Guo
Hyperinnervation in endometriosis is now well documented, but so far only a few neurotrophins have been identified. Since endometriotic stromal cells secrete thromboxane A2 (TXA2), we sought to determine whether TXA2, derived from endometriotic stromal cells, induces neurite outgrowth. Using primary sensory neurons derived from rat dorsal root ganglia (DRG) and ectopic endometrial stromal cells (EESCs) derived from human ovarian endometrioma tissues, we treated the primary neurons with different concentrations of U-46619, a stable TXA2 mimetic, and performed a neuronal growth assay...
September 29, 2016: Reproductive Sciences
https://www.readbyqxmd.com/read/27641736/associations-of-mdr1-tbxa2r-pla2g7-and-pear1-genetic-polymorphisms-with-the-platelet-activity-in-chinese-ischemic-stroke-patients-receiving-aspirin-therapy
#18
Ling-Ling Peng, Yuan-Qi Zhao, Zi-Yi Zhou, Jing Jin, Min Zhao, Xin-Meng Chen, Ling-Yan Chen, Ye-Feng Cai, Jia-Li Li, Min Huang
AIM: Aspirin resistance has an incidence of 5%-65% in patients with ischemic stroke, who receive the standard dose of aspirin, but the platelet function is inadequately inhibited, thereby leading to thrombotic events. Numerous evidence shows that thromboxane A2 receptor (TXA2 receptor, encoded by TBXA2R), lipoprotein-associated phospholipase A2 (Lp-PLA2, encoded by PLA2G7) and platelet endothelial aggregation receptor-1 (PEAR1, encoded by PEAR1) are crucial in regulating platelet activation, and P-glycoprotein (P-gp, encoded by MDR1) influences the absorption of aspirin in the intestine...
November 2016: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/27575704/facilitation-by-the-renin-angiotensin-system-of-cyclosporine-evoked-hypertension-in-rats-role-of-arterial-baroreflexes-and-vasoreactivity
#19
Suzanne A Nasser, Ramzi Sabra, Ahmed I Elmallah, Mahmoud M Mohy El-Din, Mohamed M Khedr, Mahmoud M El-Mas
AIMS: Cyclosporine (CSA) elevates blood pressure (BP) and alters arterial baroreflex sensitivity (BRS) and vasoreactivity. In this study we determined whether the renin-angiotensin system (RAS) interplays with other vasopressor pathways in mediating the CSA actions. MATERIALS AND METHODS: Whole animal and isolated vascular preparations were employed to determine the effects of pharmacologic interruption of angiotensin II (Ang II), endothelin (ET), or thromboxane (TXA2) signaling on the adverse cardiovascular effects of CSA...
October 15, 2016: Life Sciences
https://www.readbyqxmd.com/read/27565838/aspirin-and-renal-insufficiency-progression-in-patients-with-atrial-fibrillation-and-chronic-kidney-disease
#20
Daniele Pastori, Pasquale Pignatelli, Francesco Perticone, Angela Sciacqua, Roberto Carnevale, Alessio Farcomeni, Stefania Basili, Gino R Corazza, Giovanni Davì, Gregory Y H Lip, Francesco Violi
BACKGROUND: In experimental models, thromboxane (Tx)A2 reduced renal perfusion and accelerated renal failure. The aim of the study was to investigate the association between the use of aspirin, which inhibits TxA2 production, and the incidence of an estimated Glomerular Filtration Rate (eGFR) <60 and <45ml/min/1.73m(2) in patients with atrial fibrillation (AF) and chronic kidney disease (CKD). METHODS: Prospective multicentre observational cohort study including 800 anticoagulated AF patients; CKD was defined as an eGFR <90ml/min/1...
November 15, 2016: International Journal of Cardiology
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