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Monocrotaline

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https://www.readbyqxmd.com/read/28235950/the-mast-cell-b-cell-axis-in-lung-vascular-remodeling-and-pulmonary-hypertension
#1
Siegfried Breitling, Zhang Hui, Diana Zabini, Yijie Hu, Julia Hoffmann, Neil M Goldenberg, Arata Tabuchi, Roland Buelow, Claudia Dos Santos, Wolfgang Michael Kuebler
Over the past years, a critical role for the immune system and in particular, for mast cells, in the pathogenesis of pulmonary hypertension (PH) has emerged. However, the way in which mast cells promote PH is still poorly understood. Here, we investigated the mechanisms by which mast cells may contribute to PH, specifically focusing on the interaction between the innate and adaptive immune response and the role of B-cells and autoimmunity. Experiments were performed in Sprague Dawley rats and B-cell deficient JH-KO rats in the monocrotaline, sugen-hypoxia and the aortic banding model of PH...
February 24, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28213866/5-aminosalicylic-acid-attenuates-monocrotaline-induced-pulmonary-arterial-hypertension-in-rats-by-increasing-the-expression-of-nur77
#2
Ling-Yue Sun, Zong-Ye Cai, Jun Pu, Jian Li, Jie-Yan Shen, Cheng-de Yang, Ben He
The aim of this study is to investigate the effect of 5-aminosalicylic acid (5-ASA) on monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats and its molecular mechanism. Sixty male Sprague-Dawley rats (250-300 g) were evenly randomized into six groups: control group; PAH group induced by MCT intraperitoneal injection (50 mg/kg) on day 1; and four PAH groups treated for 30 days from day 2 with 5-ASA at 50 (5-ASA-50 group), 100 (5-ASA-100 group), 150 (5-ASA-150 group), and 200 mg/kg/day (5-ASA-200 group), respectively...
February 17, 2017: Inflammation
https://www.readbyqxmd.com/read/28212825/inhibition-of-ubiquitin-proteasome-function-prevents-monocrotaline-induced-pulmonary-arterial-remodeling
#3
Yanting Zhu, Yinxia Wu, Wenhua Shi, Jian Wang, Xin Yan, Qingting Wang, Ya Liu, Lan Yang, Li Gao, Manxiang Li
AIMS: Previous study has indicated that inhibition of proteasome function ameliorates the development of pulmonary arterial hypertension (PAH), while its underlying mechanisms are still unclear. This study was performed to address these issues. MATERIAL AND METHODS: Male Sprague-Dawley (SD) rats were divided into five groups: control group, PAH group, vehicle treated PAH group, MG-132 treated PAH group and bortezomib treated PAH group. PAH model was established by a single intraperitoneal injection of monocrotaline (MCT)...
February 14, 2017: Life Sciences
https://www.readbyqxmd.com/read/28202489/nicotinamide-phosphoribosyltransferase-promotes-pulmonary-vascular-remodeling-and-is-a-therapeutic-target-in-pulmonary-arterial-hypertension
#4
Jiwang Chen, Justin R Sysol, Sunit Singla, Shuangping Zhao, Aya Yamamura, Daniela Valdez-Jasso, Taimur Abbasi, Krystyna M Shioura, Sakshi Sahni, Vamsi Reddy, Arvind Sridhar, Hui Gao, Jaime Torres, Sara M Camp, Haiyang Tang, Shui Quing Ye, Suzy Comhair, Raed Dweik, Paul Hassoun, Jason X-J Yuan, Joe G N Garcia, Roberto F Machado
Background -Pulmonary arterial hypertension (PAH) is a severe and progressive disease, a hallmark of which is pulmonary vascular remodeling. Nicotinamide phosphoribosyltransferase (NAMPT), is a cytozyme which regulates intracellular NAD levels and cellular redox state, regulates histone deacetylases, promotes cell proliferation and inhibits apoptosis. We hypothesized that NAMPT promotes pulmonary vascular remodeling, and that inhibition of NAMPT could attenuate pulmonary hypertension. Methods -Plasma and mRNA and protein levels of NAMPT were measured in the lungs and isolated pulmonary artery endothelial cells (PAECs) from PAH patients, as well as in lungs of rodent models of pulmonary hypertension (PH)...
February 15, 2017: Circulation
https://www.readbyqxmd.com/read/28187784/let-7a-transfected-mesenchymal-stem-cells-ameliorate-monocrotaline-induced-pulmonary-hypertension-by-suppressing-pulmonary-artery-smooth-muscle-cell-growth-through-stat3-bmpr2-signaling
#5
Gesheng Cheng, Xingye Wang, Yongxin Li, Lu He
BACKGROUND: Cell-based gene therapy has become a subject of interest for the treatment of pulmonary arterial hypertension (PAH), a devastating disease characterized by pulmonary artery smooth muscle cell (PASMC) hyperplasia. Mesenchymal stem cells (MSCs) have been recently acknowledged as a potential cell vector for gene therapy. Here, we investigated the effect of MSC-based let-7a for PAH. METHODS: After isolation and identification of MSCs from rat bone marrow, cells were infected with recombinant adenovirus vector Ad-let-7a...
February 10, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28187460/effects-of-renal-denervation-on-monocrotaline-induced-pulmonary-remodeling
#6
Qian Liu, Jiyang Song, Dasheng Lu, Jie Geng, Zhixin Jiang, Kai Wang, Bin Zhang, Qijun Shan
Pulmonary artery hypertension (PAH) is a rapidly progressive disorder, which leads to right heart failure and even death. Overactivity of the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system accounts for the development and progression of PAH. The role of renal denervation (RDN) in different periods of PAH has not been fully elucidated. A single intraperitoneal injection of monocrotaline (MCT, 60 mg/kg) was used to induce pulmonary remodeling in male Sprague Dawley rats (n = 40). After 24-hour of MCT administration, a subset of rats underwent RDN (RDN24h, n = 10); after 2-week of MCT injection, another ten rats received RDN treatment (RDN2w, n = 10) and the left 20 rats were divided to MCT group with sham RDN operation (MCT, n = 20)...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28181133/effects-of-aerobic-exercise-training-on-metabolism-of-nitric-oxide-and-endothelin-1-in-lung-parenchyma-of-rats-with-pulmonary-arterial-hypertension
#7
A Zimmer, R B Teixeira, J H P Bonetto, R Siqueira, C C Carraro, L M Donatti, A Hickmann, I E Litvin, A E G Godoy, A S Araujo, R Colombo, Adriane Belló-Klein
Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and proliferative obstruction of pulmonary vessels, which promotes a progressive increase in pulmonary vascular resistance (PVR). The effect of exercise training on oxidative stress, metabolism, and markers of nitric oxide (NO) and endothelin-1 (ET-1) was analyzed in the lung tissue of rats with PAH induced by monocrotaline (MCT).Twenty-four Wistar rats were divided into four groups (5-7 animals): sedentary control (SC), sedentary MCT (SM), trained control (TC), and trained MCT (TM)...
February 8, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28166421/vitamin-e-and-selenium-treatment-of-monocrotaline-induced-hepatotoxicity-in-rats
#8
G Cuce, H T Canbaz, M E Sozen, F H Yerlikaya, S Kalkan
Monocrotaline (MCT) is a hepatotoxic pyrrolizidine alkaloid that is derived from plants; exposure may occur by consumption of contaminated grains, herbal teas and medicines. MCT can cause liver damage. We investigated the antioxidant effects of selenium (Se) and vitamin E against the toxic effects of MCT. Female Wistar albino rats were divided into four groups: a control group, an MCT group, an MCT + Se group, and an MCT + vitamin E group. Liver tissues were harvested, fixed, processed to paraffin and sections were cut...
February 6, 2017: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
https://www.readbyqxmd.com/read/28165252/cocktail-of-superoxide-dismutase-and-fasudil-encapsulated-in-targeted-liposomes-slows-pah-progression-at-a-reduced-dosing-frequency
#9
Nilesh Gupta, Jahidur Rashid, Eva Nozik-Grayck, Ivan F McMurtry, Kurt R Stenmark, Fakhrul Ahsan
Currently, two or more pulmonary vasodilators are used to treat pulmonary arterial hypertension (PAH), but conventional vasodilators alone cannot reverse disease progression. In this study, we tested the hypothesis that a combination therapy comprising a vasodilator plus a therapeutic agent that slows pulmonary arterial remodeling and right heart hypertrophy is an efficacious alternative to current vasodilator-based PAH therapy. Thus, we encapsulated a cocktail of superoxide dismutase (SOD), a superoxide scavenger, and fasudil, a specific rho-kinase inhibitor, into a liposomal formulation equipped with a homing peptide, CAR...
February 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28152009/superoxide-dismutase-catalase-mimetic-euk-134-prevents-diaphragm-muscle-weakness-in-monocrotalin-induced-pulmonary-hypertension
#10
Koichi Himori, Masami Abe, Daisuke Tatebayashi, Jaesik Lee, Håkan Westerblad, Johanna T Lanner, Takashi Yamada
Patients with pulmonary hypertension (PH) suffer from inspiratory insufficiency, which has been associated with intrinsic contractile dysfunction in diaphragm muscle. Here, we examined the role of redox stress in PH-induced diaphragm weakness by using the novel antioxidant, EUK-134. Male Wistar rats were randomly divided into control (CNT), CNT + EUK-134 (CNT + EUK), monocrotaline-induced PH (PH), and PH + EUK groups. PH was induced by a single intraperitoneal injection of monocrotaline (60 mg/kg body weight)...
2017: PloS One
https://www.readbyqxmd.com/read/28137936/elabela-toddler-is-an-endogenous-agonist-of-the-apelin-apj-receptor-in-the-adult-cardiovascular-system-and-exogenous-administration-of-the-peptide-compensates-for-the-downregulation-of-its-expression-in-pulmonary-arterial-hypertension
#11
Peiran Yang, Cai Read, Rhoda E Kuc, Guido Buonincontri, Mark Southwood, Rubben Torella, Paul D Upton, Alexi Crosby, Stephen J Sawiak, T Adrian Carpenter, Robert C Glen, Nicholas W Morrell, Janet J Maguire, Anthony P Davenport
BACKGROUND: -Elabela/Toddler (ELA) is a critical cardiac developmental peptide that acts through the G protein-coupled apelin receptor, despite lack of sequence similarity to the established ligand apelin. Our aim was to investigate the receptor pharmacology, expression pattern and in vivo function of ELA peptides in the adult cardiovascular system, to seek evidence for alteration in pulmonary arterial hypertension (PAH) in which apelin signaling is down-regulated, and to demonstrate attenuation of PAH severity with exogenous administration of ELA in a rat model...
January 30, 2017: Circulation
https://www.readbyqxmd.com/read/28117249/downhill-exercise-training-in-monocrotaline-injected-rats-effects-on-echocardiographic-and-haemodynamic-variables-and-survival
#12
Irina Enache, Fabrice Favret, Stéphane Doutreleau, Paola Goette Di Marco, Anne-Laure Charles, Bernard Geny, Anne Charloux
BACKGROUND: Eccentric exercise training has been shown to improve muscle force strength without excessive cardiovascular stress. Such an exercise modality deserves to be tested in pulmonary arterial hypertension. AIM: We aimed to assess the effects of an eccentric training modality on cardiac function and survival in an experimental monocrotaline-induced model of pulmonary arterial hypertension with right ventricular dysfunction. METHODS: Forty rats were randomly assigned to one of four groups: 40mg/kg monocrotaline-injected sedentary rats; 40mg/kg monocrotaline-injected eccentric-trained rats; sedentary control rats; or eccentric-trained control rats...
January 20, 2017: Archives of Cardiovascular Diseases
https://www.readbyqxmd.com/read/28095673/comparative-study-of-hepatotoxicity-of-pyrrolizidine-alkaloids-retrorsine-and-monocrotaline
#13
Xiaojing Yang, Weiwei Li, Ying Sun, Xiucai Guo, Wenlin Huang, Ying Peng, Jiang Zheng
Many pyrrolizidine alkaloids (PAs) can cause liver injury in animals and humans. Different hepatotoxic PAs can produce similar hepatotoxic effects, but the degree of their toxicities may vary widely. Retrorsine (RTS) and monocrotaline (MCT) share the same core structure (retronecine) and similar metabolic activation pathway. RTS and MCT both produced liver injury, but the former was more hepatotoxic than the latter. Enzyme kinetic study demonstrated that the value of Vmax/Km for RTS was 5.5-fold larger than that of MCT...
February 20, 2017: Chemical Research in Toxicology
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
#14
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
#15
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 W Adams, Juan Ramirez, Dominic P Behan, Anna Shifrina, Anthony Blackburn, Tina Leakakos, Yunqing Shi, Michael Morgan, Abu Sadeque, Weichao Chen, David J 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) are described. Detailed profiling of a number of analogues resulted in the identification of 5c (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 30- to 50-fold selectivity over the EP3 receptor. In our hands, its potency and efficacy are comparable or superior to MRE269 (the active metabolite of the clinical compound NS-304) with respect to in vitro IP receptor dependent cAMP accumulation assays...
February 9, 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
#16
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...
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
#17
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
#18
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...
April 2017: 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
#19
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
#20
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...
February 2017: Molecular Medicine Reports
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