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Monocrotaline

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https://www.readbyqxmd.com/read/28077433/osteoprotegerin-disruption-attenuates-hysu-induced-pulmonary-hypertension-through-integrin-%C3%AE-v%C3%AE-3-fak-akt-pathway-suppression
#1
Daile Jia, Qian Zhu, Huan Liu, Caojian Zuo, Yuhu He, Guilin Chen, Ankang Lu
BACKGROUND: Pulmonary arterial remodeling characterized by increased vascular smooth muscle proliferation is commonly seen in life-threatening disease, pulmonary arterial hypertension (PAH). Clinical studies have suggested a correlation between osteoprotegerin serum levels and PAH severity. Here, we aimed to invhestigate vascular osteoprotegerin expression and its effects on pulmonary arterial smooth muscle cell proliferation in vitro and in vivo, as well as examine the signal transduction pathways mediating its activity...
February 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28072531/discovery-of-2-1r-4r-4-4-chlorophenyl-phenyl-carbamoyl-oxy-methyl-cyclohexyl-methoxy-acetate-ralinepag-an-orally-active-prostacyclin-receptor-agonist-for-the-treatment-of-pulmonary-arterial-hypertension
#2
Thuy-Anh Tran, Bryan Kramer, Young-Jun Shin, Pureza Vallar, P Douglas Boatman, Ning Zou, Carleton R Sage, Tawfik Gharbaoui, Ashwin Krishnan, Biman Pal, Sagar R Shakya, Antonio Garrido Montalban, John Wesley Adams, Juan Ramirez, Dominic Peter Behan, Anna Shifrina, Anthony Blackburn, Tina Leakakos, Yunqing Shi, Michael Morgan, Abu Sadeque, Weichao Chen, David John Unett, Ibragim Gaidarov, Xiaohua Chen, Steve Chang, Hsin-Hui Shu, Shiu-Feng Tung, Graeme Semple
The design and synthesis of a new series of potent non-prostanoid IP receptor agonists that showed oral efficacy in the rat monocrotaline model of pulmonary arterial hypertension (PAH) is described. Detailed profiling of a number of analogues resulted in the identification of 3c (APD811, Ralinepag) that has good selectivity in both binding and functional assays with respect to most members of the prostanoid receptor family, and a more modest 40- 50-fold selectivity over the EP3 receptor. In our hands, its potency and efficacy are superior in vitro to MRE269 (the active metabolite of the clinical compound NS-304) in multiple in vitro measures of IP receptor mediated cAMP signaling...
January 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28055284/aspirin-attenuates-monocrotaline-induced-pulmonary-arterial-hypertension-in-rats-by-suppressing-the-erk-mapk-pathway
#3
Hua Gao, Yuqing Cheng, Liguo Zong, Linian Huang, Chenchen Qiao, Wei Li, Beilei Gong, Junfeng Hu, Haitao Liu, Xiaojing Wang, Chengling Zhao
This study aimed to investigate the therapeutic effects of aspirin (ASA) and its potential mechanisms of action in monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats. PAH was induced in a rat model by a single intraperitoneal (IP) injection of MCT. Saline was injected in a control group. Two weeks following MCT injection, right ventricular systolic pressure (RVSP) and systolic blood pressure (SBP) were measured in six rats from each group to confirm establishment of a PAH model. The remaining MCT-treated rats were randomly allocated to receive IP injection of saline, ASA, or ERK1/2 inhibitor PD98059...
January 5, 2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28036116/hmgb1-down-regulation-mediates-terameprocol-vascular-anti-proliferative-effect-in-experimental-pulmonary-hypertension
#4
Rita Nogueira-Ferreira, Manuel J Ferreira-Pinto, Ana Filipa Silva, Rui Vitorino, Joana Justino, Raquel Costa, Daniel Moreira-Gonçalves, Jean-François Quignard, Thomas Ducret, Jean-Pierre Savineau, Adelino F Leite-Moreira, Rita Ferreira, Tiago Henriques-Coelho
Pulmonary arterial hypertension (PAH) is a progressive disease with a poor prognosis. Pulmonary artery smooth muscle cells (PASMCs) play a crucial role in PAH pathophysiology, displaying a hyperproliferative and apoptotic-resistant phenotype. In the present study, we evaluated the potential therapeutic role of terameprocol (TMP), an inhibitor of cellular proliferation and promoter of apoptosis, in a well-established pre-clinical model of PAH induced by monocrotaline (MCT) and studied the biological pathways modulated by TMP in PASMCs...
December 30, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28030785/aldehyde-dehydrogenase-2-protects-against-oxidative-stress-associated-with-pulmonary-arterial-hypertension
#5
Tao Xu, Shuangyue Liu, Tingting Ma, Ziyi Jia, Zhifei Zhang, Aimei Wang
The cardioprotective benefits of aldehyde dehydrogenase 2 (ALDH2) are well established, although the regulatory role of ALDH2 in vascular remodeling in pulmonary arterial hypertension (PAH) is largely unknown. ALDH2 potently regulates the metabolism of aldehydes such as 4-hydroxynonenal (4-HNE), the endogenous product of lipid peroxidation. Thus, we hypothesized that ALDH2 ameliorates the proliferation and migration of human pulmonary artery smooth muscle cells (HPASMCs) by inhibiting 4-HNE accumulation and regulating downstream signaling pathways, thereby ameliorating pulmonary vascular remodeling...
December 21, 2016: Redox Biology
https://www.readbyqxmd.com/read/28011346/bucindolol-improves-right-ventricle-function-in-rats-with-pulmonary-arterial-hypertension-through-the-reversal-of-autonomic-imbalance
#6
Bruna Gazzi de Lima-Seolin, Rafael Colombo, Jéssica Hellen Poletto Bonetto, Rayane Brinck Teixeira, Luiza Mezzomo Donatti, Karina Rabello Casali, Alessandra Eifler Guerra Godoy, Isnard Elman Litvin, Paulo Cavalheiro Schenkel, Alex Sander da Rosa Araujo, Adriane Belló-Klein
Pulmonary arterial hypertension (PAH) is characterised by an elevation in afterload imposed on the right ventricle (RV), leading to hypertrophy and failure. The autonomic nervous system (ANS) plays a key role in the progression to heart failure, and the use of beta-blockers attenuates this process. The aim of this study was to verify the role of bucindolol, aβ1-, β2- and α1-blocker, on the ANS, and its association with RV function in rats with PAH. Male Wistar rats were divided into four groups: control, monocrotaline, control+bucindolol, and monocrotaline+bucindolol...
December 20, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28000863/differential-expression-of-microrna-in-the-lungs-of-rats-with-pulmonary-arterial-hypertension
#7
Tingting Xiao, Lijian Xie, Min Huang, Jie Shen
Pulmonary arterial hypertension (PAH) is a chronic disorder of the small pulmonary arteries, and the efficacy of the therapies and the prognosis remain poor. The pathobiology of PAH is complex, and needs to be elucidated by multiple approaches. The present study used a monocrotaline‑induced PAH rat model to perform a comprehensive microRNA (miRNA) microarray screening in the lungs and identified 16 downregulated miRNAs in the lungs from PAH rats. High‑enrichment gene ontology (GO) analysis identified several sets of genes, and established the miRNA‑mRNA network by outlining the interactions of miRNA and GO‑associated genes...
December 14, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27979911/atrioventricular-node-dysfunction-and-ion-channel-transcriptome-in-pulmonary-hypertension
#8
Ian P Temple, Sunil Jit R J Logantha, Mais Absi, Yu Zhang, Eleftheria Pervolaraki, Joseph Yanni, Andrew Atkinson, Maria Petkova, Gillian M Quigley, Simon Castro, Mark Drinkhill, Heiko Schneider, Oliver Monfredi, Elizabeth Cartwright, Min Zi, Tomoko T Yamanushi, Vaikom S Mahadevan, Alison M Gurney, Ed White, Henggui Zhang, George Hart, Mark R Boyett, Halina Dobrzynski
BACKGROUND: Heart block is associated with pulmonary hypertension, and the aim of the study was to test the hypothesis that the heart block is the result of a change in the ion channel transcriptome of the atrioventricular (AV) node. METHODS AND RESULTS: The most commonly used animal model of pulmonary hypertension, the monocrotaline-injected rat, was used. The functional consequences of monocrotaline injection were determined by echocardiography, ECG recording, and electrophysiological experiments on the Langendorff-perfused heart and isolated AV node...
December 2016: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/27979702/quercetin-and-baicalein-suppress-monocrotaline-induced-hepatic-sinusoidal-obstruction-syndrome-in-rats
#9
Jiaqi Zhang, Yuchen Sheng, Liang Shi, Zhiyong Zheng, Minwei Chen, Bin Lu, Lili Ji
Hepatic sinusoidal obstruction syndrome (SOS) is a rare liver disease with considerable mortality. This study is designed to observe the protection of quercetin and baicalein against monocrotaline (MCT)-induced SOS in rats and its engaged mechanism. Rats were pre-administrated with MCT (90mg/kg) to induce SOS, and 6, 30h later were orally given with quercetin and baicalein (40mg/kg) twice. Results of detecting rats with liver ascites, measuring serum transaminases, total bilirubin (TBil) and bile acids (TBA), analyzing blood cells, liver histological evaluation and scanning electron microscope observation all demonstrated the detoxification of quercetin and baicalein against MCT-induced SOS in rats...
December 13, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27941756/h2s-inhibits-pulmonary-arterial-endothelial-cell-inflammation-in-rats-with-monocrotaline-induced-pulmonary-hypertension
#10
Shasha Feng, Siyao Chen, Wen Yu, Da Zhang, Chunyu Zhang, Chaoshu Tang, Junbao Du, Hongfang Jin
This study aimed to determine whether hydrogen sulfide (H2S) inhibits pulmonary arterial endothelial inflammation in rats with monocrotaline (MCT)-induced pulmonary hypertension and its possible mechanisms. Twenty-four male Wistar rats were divided randomly into control, MCT, and MCT+H2S treatment groups. Human pulmonary arterial endothelial cells (HPAEC) were cultured and divided into four groups: control, MCT, MCT+H2S, and H2S. Pulmonary artery pressure was determined using a right cardiac catheterization procedure 3 weeks after MCT administration...
December 12, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27927914/tryptophan-hydroxylase-1-inhibition-impacts-pulmonary-vascular-remodeling-in-two-rat-models-of-pulmonary-hypertension
#11
Robert J Aiello, Patricia-Ann Bourassa, Qing Zhang, Jeffrey Dubins, Daniel R Goldberg, Stéphane De Lombaert, Marc Humbert, Christophe Guignabert, Maria A Cavasin, Timothy A McKinsey, Vishwas Paralkar
Pulmonary arterial hypertension (PAH) is a progressive disease defined by a chronic elevation in pulmonary arterial pressure with extensive pulmonary vascular remodeling and perivascular inflammation characterized by an accumulation of macrophages, lymphocytes, dendritic cells, and mast cells. Although the exact etiology of the disease is unknown, clinical as well as preclinical data strongly implicate a role for serotonin (5-HT) in the process. Here, we investigated the chronic effects of pharmacological inhibition of tryptophan hydroxylase 1 (TPH1), the rate-limiting enzyme in peripheral 5-HT biosynthesis, in two preclinical models of pulmonary hypertension (PH), the monocrotaline (MCT) rat and the semaxanib (SUGEN, Medinoah, Suzhou, China)-hypoxia rat...
February 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27916790/announcement-ueda-heart-award-for-2016
#12
(no author information available yet)
We are pleased to announce that the following 4 articles have been selected for the the UEDA Heart Awards for the Year 2016.First PlaceDelivery of Imatinib-Incorporated Nanoparticles into Lungs Suppresses the Development of Monocrotaline-Induced Pulmonary Arterial HypertensionSatoshi Akagi, Kazufumi Nakamura, Daiji Miura, Yukihiro Saito, Hiromi Matsubara, Aiko Ogawa, Tetsuya Matoba, Kensuke Egashira, Hiroshi ItoInt Heart J 2015 ; 56(3) : 354-359Second PlaceVasopressin V2 Receptor Antagonist Tolvaptan Is Effective in Heart Failure Patients With Reduced Left Ventricular Systolic Function and Low Blood PressureSatoshi Suzuki, Akiomi Yoshihisa, Takayoshi Yamaki, Koichi Sugimoto, Hiroyuki Kunii, Kazuhiko Nakazato, Yukihiko Abe, Tomiyoshi Saito, Takayuki Ohwada, Hitoshi Suzuki, Shu-ichi Saitoh, Isao Kubota, Yasuchika Takeishi, on behalf of the AVCMA investigatorsInt Heart J 2015 ; 56(2) : 213-218Third PlaceWaon Therapy Improves Quality of Life as Well as Cardiac Function and Exercise Capacity in Patients With Chronic Heart FailureMitsuo Sobajima, Takashi Nozawa, Yasutaka Fukui, Hiroyuki Ihori, Takashi Ohori, Nozomu Fujii, Hiroshi InoueInt Heart J 2015 ; 56(2) : 203-208Association of Fish Consumption-Derived Ratio of Serum n-3 to n-6 Polyunsaturated Fatty Acids and Cardiovascular Risk With the Prevalence of Coronary Artery Disease : A Cross-Sectional Pilot StudyShigemasa Tani, Atsuhiko Takahashi, Ken Nagao, Atsushi HirayamaInt Heart J 2015 ; 56(3) : 260-268November 2016International Heart Journal Association...
2016: International Heart Journal
https://www.readbyqxmd.com/read/27916219/coupling-factor-6-is-upregulated-in-monocrotaline-induced-pulmonary-arterial-hypertension-in-rats
#13
Nannan Li, Jie Yin, Weidong Cai, Jingjing Liu, Na Zhang, Suhua Yan, Lucheng Song, Xiaolu Li
BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare and fatal disease. The prostacyclin (PGI2) pathway is a well-known therapeutic target for PAH. As a novel vasoconstrictive peptide, coupling factor 6 (CF6) has been recognized as the only endogenous inhibitor of PGI2. However, the relationship between CF6 and PAH is still unknown. In this study, we investigated the involvement of CF6 in PAH in rats. METHODS: A total of 80 Sprague-Dawley rats were randomly divided into 2 groups: a control group (with saline intraperitoneally) and a monocrotaline (MCT)-treated group (with MCT 60mg/kg intraperitoneal injection)...
December 2016: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/27914611/restoration-of-uridine-5-triphosphate-suppressed-delayed-rectifying-k-currents-by-an-no-activator-kmup-1-involves-rhoa-rho-kinase-signaling-in-pulmonary-artery-smooth-muscle-cells
#14
Zen-Kong Dai, Chang-Ling Kao, Su-Ling Hsieh, Ing-Jun Chen, Bin-Nan Wu
We have demonstrated that KMUP-1 (7-[2-[4-(2-chlorobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine) blunts monocrotaline-induced pulmonary arterial hypertension by altering Ca(2+) sensitivity, K(+)-channel function, endothelial nitric oxide synthase activity, and RhoA/Rho kinase (ROCK) expression. This study further investigated whether KMUP-1 impedes uridine 5'-triphosphate (UTP)-inhibited delayed rectifying K(+) (KDR) current in rat pulmonary arteries involved the RhoA/ROCK signaling. Pulmonary artery smooth muscle cells (PASMCs) were enzymatically dissociated from rat pulmonary arteries...
December 2016: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/27912147/inhibition-of-endocan-attenuates-monocrotaline-induced-connective-tissue-disease-related-pulmonary-arterial-hypertension
#15
Haiyan Zhao, Yunxin Xue, Yun Guo, Yue Sun, Dongmei Liu, Xiaofei Wang
Connective tissue disease related pulmonary arterial hypertension (CTD-PAH) is characterized by vascular remodeling, endothelial dysfunction and inflammation. Endocan is a novel endothelial dysfunction marker. The aim of the present study was to investigate the role of endocan in CTD-PAH. Monocrotaline (MCT)-induced PAH rats were used as the CTD-PAH model. Short hairpin RNA packed in a lentiviral vector used to inhibit endocan expression was intratracheally instilled in rats prior to the MCT injection. Endocan was found to be increased in the serum and lung of MCT-induced PAH rats...
January 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/27888262/search-for-an-animal-model-to-investigate-selective-pulmonary-vasodilation
#16
Bodil Petersen, Thilo Busch, Katharina Noreikat, Lorenz Homeister, Ralf Regenthal, Udo X Kaisers
Pulmonary arterial hypertension is a life-threatening disease with a poor prognosis. Oral treatment with vasodilators is often limited by systemic hypotension. Inhalation of vasodilators offers the opportunity for selective pulmonary vasodilation. Testing selective pulmonary vasodilation by inhaled nitric oxide or alternative substances in animal models requires an increased pulmonary vascular tone. The aim of this study was to identify animal models that are suitable for investigating selective pulmonary vasodilation...
November 25, 2016: Laboratory Animals
https://www.readbyqxmd.com/read/27878490/cardiac-body-surface-potentials-in-rats-with-experimental-pulmonary-hypertension-during-ventricular-depolarization
#17
O V Suslonova, S L Smirnova, I M Roshchevskaya
The spatial and the amplitude-temporal parameters of cardiac body surface potentials were examined in female Wistar rats with experimental pulmonary hypertension during ventricular depolarization. The cardiac body surface potentials have been led from 64 subcutaneous electrodes evenly distributed across the chest surface prior to and 4 weeks after subcutaneous injection of a single dose of monocrotaline (60 mg/kg). Right ventricular hypertrophy and electrophysiological remodeling of the heart developed in rats with experimental pulmonary hypertension in 4 weeks after monocrotaline injection; these changes led to a significant increase in amplitude and temporal characteristics of the cardioelectric field on the body surface in comparison with the initial state...
November 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27873355/isoquercitrin-protects-against-pulmonary-hypertension-via-inhibiting-pasmcs-proliferation
#18
Yongtao Zhang, Yuqian Cui, Wei Deng, Hao Wang, Weidong Qin, Chengmin Huang, Chen Li, Jianning Zhang, Yuan Guo, Dawei Wu, Haipeng Guo
Pulmonary vascular remodeling is a common feature among the heterogeneous disorders that cause pulmonary arterial hypertension (PAH), and pulmonary arterial smooth muscle cells (PASMCs) proliferation impact the long-term prognosis of the patient. Isoquercitrin (IQC) is a flavonoid with anti-oxidative, anti-inflammatory and anti-proliferative activations. This study aimed to investigate whether IQC could prevent PASMCs proliferation and vascular remodeling in monocrotaline (MCT) induced PAH. Male Wistar rats were administered with vehicle or 0...
November 22, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27870162/galectin-3-contributes-to-vascular-fibrosis-in-monocrotaline-induced-pulmonary-arterial-hypertension-rat-model
#19
Xiaoyan Wang, Yanli Wang, Jinbo Zhang, Xue Guan, Minggang Chen, Yumei Li, Li Zhang
Galectin-3 (Gal-3) plays a critical role in vascular inflammation and fibrosis. The role of TGF-β1 in mediating pulmonary vascular fibrosis is well documented; thus, we suspected that Gal-3 could be an important factor in TGF-β1-induced fibrosis in pulmonary adventitial fibroblasts (PAFs). We treated rats with monocrotaline (MCT) and cultured PAFs with TGF-β1 to stimulate fibrosis. We found that MCT injection induced vessel thickening and extracellular matrix deposition in vivo. TGF-β1 stimulated the production of collagen and fibronectin (Fn) protein in vitro...
November 21, 2016: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/27847441/hypoxic-pulmonary-vasoconstriction-and-vascular-contractility-in-monocrotaline-induced-pulmonary-arterial-hypertensive-rats
#20
Hae Jin Kim, Hae Young Yoo
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vascular remodeling of pulmonary arteries (PAs) and increased vascular resistance in the lung. Monocrotaline (MCT), a toxic alkaloid, is widely used for developing rat models of PAH caused by injury to pulmonary endothelial cells; however, characteristics of vascular functions in MCT-induced PAH vary and are not fully understood. Here, we investigated hypoxic pulmonary vasoconstriction (HPV) responses and effects of various vasoconstrictors with isolated/perfused lungs of MCT-induced PAH (PAH-MCT) rats...
November 2016: Korean Journal of Physiology & Pharmacology
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