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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
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
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
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...
September 19, 2016: Acta Pharmacologica Sinica
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
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
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
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
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
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
Hideki Amano, Masaki Nakamura, Yoshiya Ito, Hiroki Kakutani, Koji Eshima, Hidero Kitasato, Shuh Narumiya, Masataka Majima
BACKGROUND: Thromboxane A synthase (TXAS) is the enzyme that converts the arachidonic acid derivative prostaglandin H2 to thromboxane A2 (TXA2). TXA2 induces platelet aggregation, vasoconstriction, and proliferation. TXAS and TXA2 receptors or thromboxane prostanoid (TP) receptors are elevated in numerous cardiovascular and inflammatory diseases. Platelets contain numerous angiogenesis stimulating factors. However, the involvement of TXAS on recovery from an ischemic condition is not well understood...
July 2016: Journal of Surgical Research
Amira Mira, Wael Alkhiary, Qinchang Zhu, Toshinori Nakagawa, Hai-Bang Tran, Yhiya M Amen, Kuniyoshi Shimizu
Isoepoxypteryxin is the major coumarin of a Japanese medicinal plant Angelica shikokiana. This research was designed to study the effect of structural changes through fungal biotransformation on the reported biological activities of isoepoxypteryxin. Among the tested microorganisms, only Cordyceps sinensis had enzymes that could catalyze the ester hydrolysis and the reductive cleavage of the epoxide ring of isoepoxypteryxin, separately, to give two more polar metabolites (+)-cis-khellactone (P1) and a new coumarin derivative (+)-cis-3'-[(2-methyl-3-hydroxybutanoyl)oxy]-4'-acetoxy-3',4'-dihydroseselin (P2), respectively...
October 2016: Chemistry & Biodiversity
Dong Zhang, Xiao-Jing Song, Shun-Yue Li, Shu-You Wang, Bing-Jun Chen, Xiao-Dong Bai, Li-Mei Tang
Imaging methods to evaluate hepatic microcirculation (HM) and liver function (LF) by directly monitoring overall liver tissue remain lacking. This study establish imaging methods for LF that combines Laser speckle perfusion imaging (LSPI) and in vivo optical imaging (IVOI) technologies to investigate changes of hepatic microcirculation and reserve function in the animals gavaged with 50% ethanol (15 ml/kg·bw) for a model of acute alcoholic liver injury (ALI), and for evaluation of electroacupuncture (EA) effect...
2016: Scientific Reports
Giovanna Petrucci, Alessandro Rizzi, Viviana Cavalca, Aida Habib, Dario Pitocco, Fabrizio Veglia, Paola Ranalli, Francesco Zaccardi, Francesca Pagliaccia, Elena Tremoli, Carlo Patrono, Bianca Rocca
The serum TXB2 (sTXB2) assay reflects the pharmacodynamics of platelet inhibition by low-dose aspirin. However, different studies reported variable sTXB2 values. sTXB2 assay requires whole blood incubation at 37 °C as a condition for optimal thrombin generation, arachidonic acid release and its metabolism by platelet cyclooxygenase-1 to form TXA2. Access to 37 °C incubation may be variably delayed, and different methods to quantitate sTXB2 may contribute to variable results between different Centers. We investigated whether delaying 37 °C incubation and/or analytical issues affect sTXB2 concentrations, biasing the assessment of aspirin responsiveness...
July 21, 2016: Thrombosis and Haemostasis
Agnieszka Kij, Lukasz Mateuszuk, Barbara Sitek, Kamil Przyborowski, Agnieszka Zakrzewska, Krystyna Wandzel, Maria Walczak, Stefan Chlopicki
The balance between vascular prostacyclin (PGI2) generated mainly via cyclooxygenase-2 (COX-2) and its physiological antagonist platelet-derived thromboxane A2 (TXA2) formed by cyclooxygenase-1 (COX-1) determines cardiovascular homeostasis. In the present work, a novel bioanalytical method for simultaneous quantification of stable plasma and urinary metabolites of PGI2 (6-keto-PGF1α, 2,3-dinor-6-keto-PGF1α) and TXA2 (TXB2, 2,3-dinor-TXB2) using ultra high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC/MS/MS) was developed...
September 10, 2016: Journal of Pharmaceutical and Biomedical Analysis
Anahita Aboonabi, Indu Singh
Thrombosis as the main complication of coronary heart disease (CHD) represents the primary cause of morbidity and mortality in patients with diabetes mellitus (DM). In the course of diabetes mellitus some coagulation abnormalities occur, that may result in a thrombogenic propensity. Aspirin (ASA) as a platelet-inhibiting agent through inactivation of Cyclooxygenase-1 (COX-1) is mostly used for the prevention and treatment of atherothrombotic disorders. ASA inhibits the COX-1 enzyme and therefore blocks platelet thromboxane A2 (TXA2) synthesis...
July 6, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Gang Du, Qiang Lin, Jinhua Wang
Aspirin is the most widely prescribed drug for the primary and secondary prevention of cardiovascular and cerebrovascular diseases. However, a large number of patients continue to experience thromboembolic events despite aspirin therapy, a phenomenon referred to as aspirin resistance or treatment failure. Aspirin resistance is often observed along with a high incidence of unstable plaque, cardiovascular events and cerebrovascular accident. Studies have shown that aspirin reduces the production of TXA2, but not totally inhibits the activation of platelets...
October 1, 2016: International Journal of Cardiology
Katie L Powell, Veronica Stevens, Dannielle H Upton, Sharon A McCracken, Ann M Simpson, Yan Cheng, Vitomir Tasevski, Jonathan M Morris, Anthony W Ashton
Intrauterine growth restriction (IUGR) is a pathology of pregnancy that results in failure of the fetus to reach its genetically determined growth potential. In developed nations the most common cause of IUGR is impaired placentation resulting from poor trophoblast function, which reduces blood flow to the fetoplacental unit, promotes hypoxia and enhances production of bioactive lipids (TXA2 and isoprostanes) which act through the thromboxane receptor (TP). TP activation has been implicated as a pathogenic factor in pregnancy complications, including IUGR; however, the role of TP isoforms during pregnancy is poorly defined...
2016: Scientific Reports
Yih-Jeng Tsai, Sheng-Po Hao, Chih-Li Chen, Wen-Bin Wu
BACKGROUND: Chronic rhinosinusitis without nasal polyps (CRSsNP) is a common chronic disease and the etiology remains unclear. Thromboxane A2 (TXA2) participates in platelet aggregation and tissue inflammation. In this study, the CXCL1/8 chemokine and TXA2-TP receptor expression in the CRSsNP mucosa was investigated. EXPERIMENTAL APPROACH: Immunohistochemistry, chemokine release assay by ELISA, RT-PCR, Real-time PCR, Western blotting, pharmacological and siRNA knockdown analysis were applied in the CRSsNP tissue specimen and cultured nasal mucosa-derived fibroblasts...
2016: PloS One
Markus Bender, David Stegner, Bernhard Nieswandt
Platelet adhesion and aggregation at sites of vascular injury are crucial for hemostasis; however, under pathological conditions, they can cause myocardial infarction and stroke. Platelet adhesion is mediated by binding of the glycoprotein (GP)Ib-V-IX complex to immobilized von Willebrand factor (vWF), thereby enabling the interaction of GPVI with exposed collagen and subsequent platelet activation. This process is reinforced by locally produced thrombin and platelet-derived adenosine diphosphate (ADP) and thromboxane A2 (TxA2), leading to a conformational change of integrins from a low- to a high-affinity state, which allows firm platelet adhesion and aggregation...
June 23, 2016: Platelets
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