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https://www.readbyqxmd.com/read/28712920/amelioration-of-cirrhotic-portal-hypertension-by-targeted-cyclooxygenase-1-sirna-delivery-to-liver-sinusoidal-endothelium-with-polyethylenimine-grafted-hyaluronic-acid
#1
Liteng Lin, Mingyue Cai, Shaohui Deng, Wensou Huang, Jingjun Huang, Xinghua Huang, Mingsheng Huang, Yong Wang, Xintao Shuai, Kangshun Zhu
Portal hypertension (PH), a leading cause of mortality in cirrhosis, lacks effective clinical therapeutic strategies. The increased thromboxane A2 (TXA2), derived primarily from the upregulation of cyclooxygenase-1 (COX-1) in cirrhotic liver sinusoidal endothelial cells (LSECs), is responsible for hepatic endothelial dysfunction and PH. Thus, blocking the COX-1 pathway in cirrhotic LSECs may benefit the treatment of PH. In this study, hyaluronate-graft-polyethylenimine (HA-PEI) was synthesized for the targeted delivery of COX-1 siRNA to LSECs...
July 13, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28712765/losartan-reverses-cox-2-dependent-vascular-dysfunction-in-offspring-of-hyperglycaemic-rats
#2
Diego Barbosa de Queiroz, Fernanda Elizabethe Ramos-Alves, Juliana Santos-Rocha, Gloria Pinto Duarte, Fabiano Elias Xavier
AIMS: This study examined whether chronic treatment with losartan, an angiotensin II type 1 receptor (AT1R) antagonist, might reverse COX-2-mediated vascular dysfunction in mesenteric resistance arteries (MRA) from offspring of hyperglycaemic rats. MATERIALS AND METHODS: Male 12-month-old offspring of hyperglycaemic (O-DR) and normoglycaemic (O-CR) rats were treated with losartan (15mg·kg·day(-1)) during 2months. Third order MRA of untreated and losartan-treated O-DR and O-CR were mounted in wire myograph for isometric tension measurements...
July 13, 2017: Life Sciences
https://www.readbyqxmd.com/read/28705934/gq-pathway-regulates-proximal-c-type-lectin-like-receptor-2-clec-2-signaling-in-platelets
#3
Rachit Badolia, Vaishali Inamdar, Bhanu Kanth Manne, Carol Dangelmaier, Satya P Kunapuli
Platelets play a key role in the physiological hemostasis or pathological process of thrombosis. Rhodocytin, an agonist of the C-type lectin like receptor-2 (CLEC-2), elicits powerful platelet activation signals in conjunction with Src family kinases (SFKs), spleen tyrosine kinase (Syk), and phospholipase γ2 (PLCγ2). Previous reports have shown that rhodocytin-induced platelet aggregation depends on secondary mediators such as thromboxane (TxA2) and ADP, which are agonists for G protein coupled receptors (GPCRs) on platelets...
July 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28704403/genetic-variants-of-ptgs2-txa2r-and-txas1-are-associated-with-carotid-plaque-vulnerability-platelet-activation-and-txa2-levels-in-ischemic-stroke-patients
#4
Xingyang Yi, Jing Lin, Hua Luo, Chun Wang, Yingying Liu
Eicosanoids may play a role in ischemic stroke. However, the associations of variants in cyclooxygenase (COX) pathway genes and interaction among these variants with carotid plaque vulnerability are not fully understood. In present study, twelve variants in COX pathway genes were examined using matrix-assisted laser desorption ionization time-of-flight mass spectrometry method in 396 patients with ischemic stroke and 291 controls. Platelet aggregation, platelet-leukocyte aggregates, and urine 11-dehydrothromboxane B2 (11-dTxB2) were also measured...
2017: PloS One
https://www.readbyqxmd.com/read/28686356/relaxing-responses-to-hydrogen-peroxide-and-nitric-oxide-in-human-pericardial-resistance-arteries-stimulated-with-endothelin-1
#5
Thomas M Leurgans, Maria Bloksgaard, Akhmadjon Irmukhamedov, Lars P Riber, Jo G R De Mey
In human pericardial resistance arteries, effects of the endothelium-dependent vasodilator bradykinin are mediated by NO during contraction induced by K(+) or the TxA2 analogue U46619 and by H2 O2 during contraction by endothelin-1 (ET-1), respectively. We tested the hypotheses that ET-1 reduces relaxing effects of NO and increases those of H2 O2 in resistance artery smooth muscle of patients with cardiovascular disease. Arterial segments, dissected from the parietal pericardium of 39 cardiothoracic surgery patients, were studied by myography during amplitude-matched contractions induced by K(+) , the TXA2 analogue U46619 or ET-1...
July 7, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28662100/mir-146a-mir-146b-and-mir-155-increase-expression-of-il-6-and-il-8-and-support-hsp10-in-an-in-vitro-sepsis-model
#6
Dagmar Pfeiffer, Eva Roßmanith, Ingrid Lang, Dieter Falkenhagen
microRNAs (miRNAs) play an essential role in inflammation processes including sepsis. This study aimed to identify miRNAs as candidates for therapies that are involved in the innate immune response and to assess their potential functions in the activation of the endothelium. We stimulated THP-1 monocytes with 10 ng/ml LPS for 4 h and used the supernatant for the stimulation of human umbilical vein endothelial cells (HUVEC) or human pulmonary microvascular endothelial cells (HPMEC) for 16 h. miRNA array analysis (of 1,891 miRNAs) identified a 1...
2017: PloS One
https://www.readbyqxmd.com/read/28650494/chemical-characteristics-of-an-ilex-kuding-tea-polysaccharide-and-its-protective-effects-against-high-fructose-induced-liver-injury-and-vascular-endothelial-dysfunction-in-mice
#7
Xichuan Zhai, Daoyuan Ren, Yiyang Luo, Yuanyuan Hu, Xingbin Yang
The present study was designed to investigate the protective effects of Ilex Kuding tea polysaccharides (IKTP) on high fructose (HF)-induced liver injury and vascular endothelial dysfunction in mice. IKTP were identified as acidic heteropolysaccharides by FT-IR and HPLC. Healthy male Kunming mice fed 20% fructose in drinking water for 8 consecutive weeks significantly displayed dyslipidemia, hepatic steatosis, oxidative stress and vascular endothelial dysfunction. However, continuous administration of IKTP at 200, 400 and 800 mg per kg bw in HF-fed mice could prevent the damage caused by HF-diets, especially at dosages of 400 and 800 mg per kg bw (p < 0...
July 19, 2017: Food & Function
https://www.readbyqxmd.com/read/28645780/salvia-miltiorrhiza-bunge-danshen-extract-attenuates-permanent-cerebral-ischemia-through-inhibiting-platelet-activation-in-rats
#8
Yu-Xiang Fei, Si-Qi Wang, Li-Jian Yang, Yan-Ying Qiu, Yi-Ze Li, Wen-Yuan Liu, Tao Xi, Wei-Rong Fang, Yun-Man Li
ETHNOPHARMACOLOGICAL RELEVANCE: Danshen is a crude herbal drug isolated from dried roots of Salvia miltiorrhiza Bunge. This plant is widely used in oriental medicine for the treatment of cardiovascular and cerebrovascular diseases. The supercritical CO2 extract from Danshen (SCED) (57.85%, 5.67% and 4.55% for tanshinone IIA, tanshinone I and cryptotanshinone respectively) was studied in this article, whose potential molecular mechanism remains unclear, especially in anti-thrombosis. AIM OF THE STUDY: The present study was designed to observe the protective effect of SCED on ischemic stroke in rats and to explore the underlying anti-thrombosis mechanism...
June 20, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28630527/a-promising-approach-to-integrally-evaluate-the-disease-outcome-of-cerebral-ischemic-rats-based-on-multiple-biomarker-crosstalk
#9
Guimei Ran, Yixuan Wang, Haochen Liu, Chunxiang Wei, Tao Zhu, Haidong Wang, Hua He, Xiaoquan Liu
PURPOSE: The study was designed to evaluate the disease outcome based on multiple biomarkers related to cerebral ischemia. METHODS: Rats were randomly divided into sham, permanent middle cerebral artery occlusion, and edaravone-treated groups. Cerebral ischemia was induced by permanent middle cerebral artery occlusion surgery in rats. To form a simplified crosstalk network, the related multiple biomarkers were chosen as S100β, HIF-1α, IL-1β, PGI2, TXA2, and GSH-Px...
2017: Disease Markers
https://www.readbyqxmd.com/read/28623974/increased-placental-phospholipase-a2-gene-expression-and-free-f2-isoprostane-levels-in-response-to-oxidative-stress-in-preeclampsia
#10
M Brien, J Larose, K Greffard, P Julien, J F Bilodeau
Vasoactive eicosanoids such as thromboxane (TX) A2 and F2-isoprostanes (F2-isoPs) were shown to be increased in the preeclamptic placenta. Only one of the 64 possible isomers of F2-isoPs derived from the oxidation of arachidonic acid was investigated in the placenta so far. F2-isoPs are released from membrane phospholipids by phospholipases A2 (PLA2) and were shown to act on the TXA2 receptor (TBXA2R). However, the PLA2 deregulated in preeclampsia (PE) remains to be determined. In this study, we analyzed the concentrations of six isomers of F2-isoPs; 8-iso-PGF2α, 8-iso-15(R)-PGF2α, 15(R)-PGF2α, iPF2α-IV, iPF2α-VI, 5-iPF2α-VI and the concentrations of the stable metabolites of TXA2, TXB2, by high performance liquid chromatography coupled with tandem mass spectrometry in placentas of PE (n = 17) and normotensive (n = 15) pregnancies according to the biopsy site: peri-insertion or periphery...
July 2017: Placenta
https://www.readbyqxmd.com/read/28621447/metformin-prevents-vascular-prostanoid-release-alterations-induced-by-a-high-fat-diet-in-rats
#11
H J Lee, S M Cantú, A S Donoso, M R Choi, H A Peredo, A M Puyó
Perivascular adipose tissue dysfunction induced by high-fat feeding leads to alterations in the modulation of inflammation, contractile activity of the vascular smooth muscle and endothelial function, all risk factors in the development of hypertension. Metformin, an activator of AMP-activated protein kinase (AMPK), is currently the first-line drug treatment for type 2 diabetes (T2DM) and metabolic syndrome. Besides its glucose-lowering effect, there is an interest in actions of this drug with potential relevance in cardiovascular diseases...
June 16, 2017: Autonomic & Autacoid Pharmacology
https://www.readbyqxmd.com/read/28580812/platelet-reactivity-in-stable-cardiovascular-patients-with-chronic-kidney-disease
#12
Thomas A Mavrakanas, Ahsan Alam, Jean-Luc Reny, Pierre Fontana
The study aimed to evaluate antiplatelet drug responsiveness in stable outpatients with cardiovascular disease and chronic kidney disease (CKD) and examine whether impaired antiplatelet drug responsiveness is associated with worse clinical outcomes in this population. Stable cardiovascular patients (n = 771) were enrolled at least one month after an acute ischemic atherothrombotic event. Antiplatelet drug responsiveness was assessed with specific assays (serum TxA2 for aspirin, the VASP assay for clopidogrel) and other aggregation-based assays using different agonists...
June 5, 2017: Platelets
https://www.readbyqxmd.com/read/28556994/hyperglycemia-in-pregnant-rats-causes-gender-related-vascular-dysfunction-in-adult-offspring-role-of-cyclooxygenase-2
#13
Francine Gomes de Sá, Diego Barbosa de Queiroz, Fernanda Elizabethe Ramos-Alves, Juliana Santos-Rocha, Odair Alves da Silva, Hicla Steffany Moreira, Geórgia Andrade Leal, Marcelo Aurélio da Rocha, Gloria Pinto Duarte, Fabiano Elias Xavier
Exposure to maternal hyperglycemia induces hypertension and vascular dysfunction in adult male offspring. Because female offspring from several fetal programming models are protected from the effects of fetal insult, in this study we analyzed possible differences relative to gender in blood pressure and vascular function in hyperglycemia-programmed offspring. Hyperglycemia was induced on gestation day 7 (streptozotocin, 50 mg.kg(-1) ). Blood pressure, acetylcholine and phenylephrine/noradrenaline responses were analyzed in aorta and mesenteric resistance arteries (MRA) of 3-, 6- and 12-month-old male and female offspring...
May 30, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28556909/altered-postcapillary-and-collecting-venular-reactivity-in-skeletal-muscle-with-metabolic-syndrome
#14
Kent A Lemaster, Zahra Farid, Robert W Brock, Carl D Shrader, Daniel Goldman, Dwayne N Jackson, Jefferson C Frisbee
While research into vascular outcomes of the metabolic syndrome has focused on arterial/arteriolar and capillary levels, investigation into venular function and how this impacts responses has received little attention. Using the in situ cremaster muscle of obese Zucker rats (OZR; with leans (LZR) as controls), we determined indices of venular function. At ∼17 weeks of age, skeletal muscle post-capillary venular density was reduced by ∼20% in LZR vs. OZR, although there was no evidence of remodeling of the venular wall...
May 30, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28544540/serum-adrenomedullin-and-urinary-thromboxane-b2-help-early-categorizing-acute-kidney-injury-in-de-compensated-cirrhotic-patients-a-prospective-cohort-study
#15
Chih-Wei Liu, Chia-Chang Huang, Hung-Cheng Tsai, Yen-Bo Su, Shiang-Fen Huang, Kuei-Chuan Lee, Yun-Cheng Hsieh, Tzu-Hao Li, Chang-Youh Tsai, Lee-Won Chong, Shuo-Ming Ou, Ying-Ying Yang, Wen-Chien Fan, Ming-Chih Hou, Han-Chieh Lin, Shou-Dong Lee
AIMS: Increases in the systemic vasodilator adrenomedullin and the renal vasoconstrictors thromboxane A2 (TXA2 ) in cirrhotic patients are pathogenic factors for the development of functional acute-kidney-injury, including pre-renal azotemia (PRA) and hepatorenal syndrome (HRS), which is associated with high mortality. This study aims to find biomarkers which can diagnose HRS in early stage for treating it as soon as possible. METHODS: Acute decompensated cirrhotic patients who had been admitted to hospital were enrolled in this prospective cohort study...
May 20, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28513223/activation-of-thromboxane-a2-receptors-mediates-endothelial-dysfunction-in-diabetic-mice
#16
Xiaona Xie, Wanchun Sun, Jun Wang, Xiaoou Li, Xiaofeng Liu, Ning Liu
BACKGROUND: Diabetes is one of high-risk factors for cardiovascular disease. Improvement of endothelial dysfunction in diabetes reduces vascular complications. However, the underlying mechanism needs to be uncovered. This study was conducted to elucidate whether and how thromboxane A2 receptor (TPr) activation contributes to endothelial dysfunction in diabetes. METHODS AND RESULTS: Exposure of human umbilical vein endothelial cells (HUVECs) to either TPr agonists, two structurally related thromboxane A2 (TxA2) mimetics, significantly reduced phosphorylations of endothelial nitric oxide synthase (eNOS) at Ser(1177) and Akt at Ser(473)...
2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28492699/lipopolysaccharide-as-trigger-of-platelet-aggregation-via-eicosanoid-over-production
#17
Cristina Nocella, Roberto Carnevale, Simona Bartimoccia, Marta Novo, Roberto Cangemi, Daniele Pastori, Camilla Calvieri, Pasquale Pignatelli, Francesco Violi
The effect of lipopolysaccharide (LPS) on platelet aggregation is still controversial. We performed in vitro and ex vivo studies in controls and in patients with community-acquired pneumonia (CAP) to assess the effect of LPS on platelet activation (PA). LPS (15-100 pg/ml) significantly increased PA only if combined with sub-threshold concentrations (STC) of collagen or ADP; this effect was associated with increased platelet H2O2 production, Nox2 activation, PLA2 phosphorylation, thromboxane (Tx)A2 and 8-iso-PGF2α-III, and was inhibited by aspirin, TxA2 receptor antagonist or by Toll-like receptor 4 blocking peptide (TLR4bp)...
May 11, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28465708/rs5911-and-rs3842788-genetic-polymorphism-blood-stasis-syndrome-and-plasma-txb2-and-hs-crp-levels-are-associated-with-aspirin-resistance-in-chinese-chronic-stable-angina-patients
#18
Mei Xue, Xuesong Yang, Lin Yang, Na Kou, Yu Miao, Mingming Wang, Junhua Ren, Quanli Zhao
The identification of single nucleotide polymorphisms (SNPs) related to aspirin resistance (AR) is of great significance for the explanation why some individuals demonstrate an incomplete response to aspirin and for optimizing the antiplatelet therapy strategy. The study was designed to investigate the possible associated genetic markers and clinical factors of AR for Chinese patients with chronic stable angina after PCI and to analyze the association between TXA2, PGI2, hs-CRP level, AR, and gene polymorphisms...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28450284/eets-promote-hypoxic-pulmonary-vasoconstriction-via-constrictor-prostanoids
#19
Sharath Kandhi, Bin Zhang, Ghezal Froogh, Jun Qin, Norah Alruwali, Yicong Le, Yang-Ming Yang, Sung Hee Hwang, Bruce D Hammock, Michael S Wolin, An Huang, Dong Sun
To test the hypothesis that epoxyeicosatrienoic acids (EETs) facilitate pulmonary responses to hypoxia, male wild type (WT) and soluble epoxide hydrolase knockout (sEH-KO) mice, and WT mice chronically fed a sEH inhibitor (t-TUCB; 1mg/kg/day) were used. Right ventricular systolic pressure (RVSP) was recorded under control and hypoxic conditions. The control RVSP was comparable among all groups. However, hypoxia elicited increases in RVSP in all groups with predominance in sEH-KO and t-TUCB-treated mice. 14,15-EEZE (EET antagonist) attenuated the hypoxia-induced greater elevation of RVSP in sEH-deficient mice, suggesting an EET-mediated increment...
April 27, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28445779/the-acute-cardiorespiratory-effects-of-centrally-injected-arachidonic-acid-the-mediation-of-prostaglandin-e-d-and-f2%C3%AE
#20
Leman Gizem Erkan, Burcin Altinbas, Gokcen Guvenc, Begum Aydin, Nasir Niaz, Murat Yalcin
Arachidonic acid (AA), which is released from synaptic membrane phospholipid by neuroreceptor-initiated activation of phospholipase A2, is abundant in the brain and works as a neurotransmitter and/or neuromodulator in the central nervous system. Recently we reported that centrally injected AA generated pressor and hyperventilation effects by activating thromboxane A2 (TXA2) signaling pathway. The present study was designed to investigate the mediation of other metabolites of AA such as prostaglandin (PG) D, PGE and PGF2α alongside TXA2 in the AA-evoked cardiorespiratory effects in anaesthetized rats...
April 23, 2017: Respiratory Physiology & Neurobiology
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