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https://www.readbyqxmd.com/read/28069828/lpa1-receptor-mediated-thromboxane-a2-release-is-responsible-for-lysophosphatidic-acid-induced-vascular-smooth-muscle-contraction
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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)...
September 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27688244/endometriosis-derived-thromboxane-a2-induces-neurite-outgrowth
#13
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
#14
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
#15
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
#16
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
https://www.readbyqxmd.com/read/27562142/thromboxane-a2-exacerbates-acute-lung-injury-via-promoting-edema-formation
#17
Koji Kobayashi, Daiki Horikami, Keisuke Omori, Tatsuro Nakamura, Arisa Yamazaki, Shingo Maeda, Takahisa Murata
Thromboxane A2 (TXA2) is produced in the lungs of patients suffering from acute lung injury (ALI). We assessed its contribution in disease progression using three different ALI mouse models. The administration of hydrochloric acid (HCl) or oleic acid (OA)+ lipopolysaccharide (LPS) caused tissue edema and neutrophil infiltration with TXA2 production in the lungs of the experimental mice. The administration of LPS induced only neutrophil accumulation without TXA2 production. Pretreatment with T prostanoid receptor (TP) antagonist attenuated the tissue edema but not neutrophil infiltration in these models...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27519725/anti-platelet-therapy-is-efficacious-in-treating-endometriosis-induced-in-mouse
#18
Sun-Wei Guo, Ding Ding, Xishi Liu
In light of recent findings showing that platelets play important roles in the development of endometriosis in general and in fibrogenesis in particular, this study investigated the efficacy of Ozagrel, a TXA2 synthase inhibitor, in a murine model of endometriosis. In addition, another mouse experiment was conducted to evaluate the effect of timing of platelet depletion and of sequential depletion of platelets and macrophages on the development of endometriosis. It was found that both the Ozagrel treatment and different platelet depletion schemes resulted in significant reduction in lesion growth (all P-values <0...
October 2016: Reproductive Biomedicine Online
https://www.readbyqxmd.com/read/27511998/11-dehydro-thromboxane-b2-levels-after-percutaneous-transluminal-angioplasty-in-patients-with-peripheral-arterial-occlusive-disease-during-a-one-year-follow-up-period
#19
P Maga, M Sanak, J Jawien, B Rewerska, M Maga, A Wachsmann, M Koziej, I Gregorczyk-Maga, R Nizankowski
The aim of our study was to determine if the generation of thromboxane is altered in patients with peripheral arterial occlusive disease following percutaneous transluminal angioplasty (PTA) during a one year follow-up period. In this study, 175 patients diagnosed with peripheral arterial occlusive disease (PAOD) and demonstrating short-distance claudication or ischemic rest pain, requiring PTA in either the iliac, femoral, or popliteal arteries, were enrolled. The excretion of 11-dehydro thromboxane B2 (TXB2) was measured in urine samples by high-performance liquid chromatography-mass spectrometry and recalculated based on the creatinine concentration...
June 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/27508651/-op-3b-02-ageing-and-lack-of-estrogens-activates-cyclooxygenases-pathway-increasing-superoxide-anion-production-in-response-to-thromboxane-a2
#20
S Novella, X Vidal-Gómez, A Mompeón, D Pérez-Cremades, G Segarra, P Medina, C Hermenegildo
OBJECTIVE: The role of ageing in the development of vascular disease is currently associated with a rise in oxidative stress. Thromboxane A2 (TXA2) is an inflammatory and oxidant endogenous vasoconstrictor which action increases with ageing and lack of estrogens, both conditions found in menopause. Our aim was to determine superoxide anion (O2-) levels in response to TXA2 in aortic vascular tissue from senescent and ovariectomized mice and the role of cyclooxygenase as source of O2-. DESIGN AND METHOD: Senescence accelerated mice (SAM) were used in this study...
September 2016: Journal of Hypertension
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