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Endothelin inhibitor

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https://www.readbyqxmd.com/read/30007232/erythropoietin-alleviates-hyperglycaemia-associated-inflammation-by-regulating-macrophage-polarization-via-the-jak2-stat3-signalling-pathway
#1
Jinjin Cui, Fengyun Zhang, Wei Cao, Yongshun Wang, Jingjin Liu, Xinxin Liu, Tao Chen, Ling Li, Jinwei Tian, Bo Yu
BACKGROUND: Erythropoietin (EPO), which is clinically used for renal anaemia, reportedly exerts beneficial pleiotropic effects in atherosclerosis. This aim of this study was to investigate the effects of EPO on macrophage inflammation and polarization under hyperglycaemic conditions and to identify the effects of EPO-treated macrophage supernatants (SNs) on endothelial cell (EC) function. METHODS: Peritoneal macrophages (pMΦs) were isolated from normal, diabetic or EPO-injected mice...
July 11, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/30005860/therapy-of-scleroderma-renal-crisis-state-of-the-art
#2
REVIEW
Elisabetta Zanatta, Pamela Polito, Mariangela Favaro, Maddalena Larosa, Piero Marson, Franco Cozzi, Andrea Doria
Scleroderma renal crisis (SRC) is an uncommon but still life-threatening manifestation of systemic sclerosis (SSc). The incidence of SRC has decreased in the last few decades, probably due to a widespread use of vasodilators in SSc patients. It is well-recognized that exposure to different drugs can trigger SRC (corticosteroids, cyclosporine) or prevent its occurrence (iloprost, calcium channel blockers). The prognosis of this life-threatening manifestation has not substantially improved since 1980s, when ACE-inhibitors were introduced in its treatment...
July 10, 2018: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29996135/palmitic-acid-increases-endothelin-1-expression-in-vascular-endothelial-cells-through-the-induction-of-endoplasmic-reticulum-stress-and-protein-kinase-c-signaling
#3
Juan Zhang, Wen-Shu Zhao, Xin Wang, Lin Xu, Xin-Chun Yang
OBJECTIVE: We investigated the regulation of endothelin-1 (ET-1) expression in in vivo high-fat diet (HFD)-fed mice and in vitro cultured human aortic endothelial cells (HAECs). METHODS: Male C57BL/6 mice were fed on standard chow, serum was prepared, and ET-1 levels were analyzed using an ELISA kit. Quantitative PCR was performed using iQ SYBR Green Supermix. Statistical significance was assessed using SPSS, with p < 0.05 considered significant. RESULTS: The serum ET-1 content and endothelial expression of ET-1 mRNA were increased in the HFD-fed mice compared to the chow-fed control mice...
July 11, 2018: Cardiology
https://www.readbyqxmd.com/read/29984882/association-between-smoking-status-assessed-with-plasma-cotinine-and-inflammatory-and-endothelial-biomarkers-in-hiv-positive-and-hiv-negative-individuals
#4
M G Ahlström, A Knudsen, H Ullum, J Gerstoft, A Kjaer, A-M Lebech, P Hasbak, N Obel
OBJECTIVES: Smoking is a major contributor to mortality and morbidity in HIV-positive individuals. Our primary objective was to evaluate the association between smoking status determined by plasma cotinine (P-cotinine) concentration and inflammatory and endothelial biomarkers in HIV-positive versus HIV-negative individuals. METHODS: We studied eight inflammatory/endothelial biomarkers [high-sensitivity C-reactive protein (hsCRP), E-selectin, soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), matrix metallopeptidase 9 (MMP-9), myeloperoxidase (MPO), tissue type plasminogen activator inhibitor 1 (tPAI) and endothelin] in 105 HIV-positive individuals and 105 HIV-negative individuals matched on age, sex and self-reported smoking status...
July 9, 2018: HIV Medicine
https://www.readbyqxmd.com/read/29962965/inhibition-of-prostate-smooth-muscle-contraction-by-inhibitors-of-polo-like-kinases
#5
Martin Hennenberg, Paul Kuppermann, Qingfeng Yu, Annika Herlemann, Alexander Tamalunas, Yiming Wang, Beata Rutz, Anna Ciotkowska, Frank Strittmatter, Christian G Stief, Christian Gratzke
Background: Prostate smooth muscle contraction plays an important role for pathophysiology and treatment of male lower urinary tract symptoms (LUTS) but is incompletely understood. Because the efficacy of available medication is limited, novel options and improved understanding of prostate smooth muscle contraction are of high demand. Recently, a possible role of polo-like kinase 1 (PLK1) has been suggested for smooth muscle contraction outside the lower urinary tract. Here, we examined effects of PLK inhibitors on contraction of human prostate tissue...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29954114/connexin-43-plays-a-role-in-pulmonary-vascular-reactivity-in-mice
#6
Myo Htet, Jane E Nally, Andrew Shaw, Bradley E Foote, Patricia E Martin, Yvonne Dempsie
Pulmonary arterial hypertension (PAH) is a chronic condition characterized by vascular remodeling and increased vaso-reactivity. PAH is more common in females than in males (~3:1). Connexin (Cx)43 has been shown to be involved in cellular communication within the pulmonary vasculature. Therefore, we investigated the role of Cx43 in pulmonary vascular reactivity using Cx43 heterozygous ( Cx43+/&minus; ) mice and 37,43 Gap27, which is a pharmacological inhibitor of Cx37 and Cx43. Contraction and relaxation responses were studied in intra-lobar pulmonary arteries (IPAs) derived from normoxic mice and hypoxic mice using wire myography...
June 27, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29950821/elicitation-of-health-state-utilities-associated-with-the-mode-of-administration-of-drugs-acting-on-the-prostacyclin-pathway-in-pulmonary-arterial-hypertension
#7
Evan W Davies, Samuel Llewellyn, Amélie Beaudet, Charlotte E Kosmas, Wendy Gin-Sing, Helen A Doll
Introduction: Pulmonary arterial hypertension (PAH) is a rare, incurable disease associated with decreased life expectancy and a marked impact on quality of life (QoL). There are three classes of drugs available for treatment: endothelin receptor antagonists (ERA), drugs acting on nitric oxide pathway (riociguat and phosphodiesterase type 5 inhibitors [PDE5i]), and drugs acting on prostacyclin pathway. The latter have widely different modes of administration - continuous intravenous infusion, continuous subcutaneous infusion, inhaled, and oral - each associated with variable treatment burden, and implications for health economic assessment...
2018: Patient Preference and Adherence
https://www.readbyqxmd.com/read/29947537/endothelin-a-receptor-blockade-improves-endothelium-dependent-relaxation-in-obese-woman
#8
K Gradin, B Persson
Hypertension in obesity is associated with increased insulin resistance, vascular mass and body mass index (BMI). The purpose of the study was to visualize endothelin-1 (ET-1) mediated constriction in arteries isolated from subcutaneous adipose tissue from obese hypertensive women previously operated by gastric bypass. Functional studies were conducted in a microvascular myograph. Expressed as percentage of contraction elicited by 124 mM KCl concentration-response curves for ET-1 were shifted leftward in arteries from obese hypertensive patients compared to healthy normotensive subjects...
June 27, 2018: Physiological Research
https://www.readbyqxmd.com/read/29947527/new-drugs-and-emerging-therapeutic-targets-in-the-endothelin-signaling-pathway-and-prospects-for-personalized-precision-medicine
#9
A P Davenport, R E Kuc, C Southan, J J Maguire
During the last thirty years since the discovery of endothelin-1, the therapeutic strategy that has evolved in the clinic, mainly in the treatment of pulmonary arterial hypertension, is to block the action of the peptide either at the ET(A) subtype or both receptors using orally active small molecule antagonists. Recently, there has been a rapid expansion in research targeting ET receptors using chemical entities other than small molecules, particularly monoclonal antibody antagonists and selective peptide agonists and antagonists...
June 27, 2018: Physiological Research
https://www.readbyqxmd.com/read/29931399/tyrosine-kinase-inhibitor-induced-hypertension
#10
REVIEW
Megha Agarwal, Nidhi Thareja, Melody Benjamin, Andre Akhondi, George D Mitchell
PURPOSE OF REVIEW: The purpose of this paper is to identify commonly used tyrosine kinase inhibitors (TKIs) that are associated with hypertension, primarily, vascular endothelial growth factor (VEGF) signaling pathway (VSP) inhibitors. We review the incidence, mechanism, and strategies for management of TKI-induced HTN. We hope to provide clinicians with guidance on how to manage similar clinical scenarios. RECENT FINDINGS: Many of the newer VSP inhibitors are reviewed here, including cediranib, axitinib, pazopanib, and ponatinib...
June 21, 2018: Current Oncology Reports
https://www.readbyqxmd.com/read/29924890/targeting-mmp-13-in-bronchial-epithelial-repair
#11
Christopher Howell, James R Smith, Janis K Shute
BACKGROUND: Viral infection of the bronchial epithelium disrupts the barrier properties of the epithelium in healthy individuals and those with lung disease. Repair of the bronchial epithelium is dependent of the formation of a provisional fibrin matrix and migration of epithelial cells to cover denuded areas, followed by proliferation and differentiation. OBJECTIVE: The objective was to test the hypothesis that poly I:C, a model of viral infection, limits epithelial repair through the stimulated release of matrix metalloproteinase-13 (MMP-13)...
June 20, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29906506/high-resolution-crystal-structure-of-substrate-free-human-neprilysin
#12
Stephen Moss, Vasanta Subramanian, K Ravi Acharya
Neprilysin is a transmembrane M13 zinc metalloprotease responsible for the degradation of several biologically active peptides including insulin, enkephalin, substance P, bradykinin, endothelin-1, neurotensin and amyloid-β. The protein has received attention for its role in modulating blood pressure responses with its inhibition producing an antihypertensive response. To date, several inhibitor bound crystal structures of the human neprilysin extracellular domain have been determined, but, a structure free of bound inhibitor or substrate has yet to be reported...
June 12, 2018: Journal of Structural Biology
https://www.readbyqxmd.com/read/29904040/a-pilot-trial-to-examine-the-changes-in-carotid-arterial-inflammation-in-renal-transplant-recipients-as-assessed-by-18f-fluorodeoxyglucose-18f-fdg-positron-emission-tomography-computed-tomography-pet-ct
#13
Hye Eun Yoon, Yaeni Kim, Sang Dong Kim, Jin Kyoung Oh, Yong-An Chung, Seok Joon Shin, Chul Woo Yang, Suk Min Seo
BACKGROUND Inflammatory activity of the artery can be assessed by measuring 18F-fluorodeoxyglucose (18F-FDG) uptake with positron emission tomography computed tomography (PET/CT). Improvement in vascular function after renal transplantation has been reported, but no studies have used 18F-FDG PET/CT to examine the changes in vascular inflammation. This study investigated the changes in the inflammatory activity in the carotid artery after renal transplantation in patients with chronic kidney disease (CKD). MATERIAL AND METHODS 18F-FDG PET/CT was performed before and at 4 months after transplantation...
June 15, 2018: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/29901088/fasudil-preserves-lung-endothelial-function-and-reduces-pulmonary-vascular-remodeling-in-a-rat-model-of-end%C3%A2-stage-pulmonary-hypertension-with-left-heart-disease
#14
Rulin Zhuang, Jinfu Wu, Fang Lin, Lu Han, Xiaoting Liang, Qingshu Meng, Yuyu Jiang, Zhulin Wang, Aixue Yue, Yuying Gu, Huimin Fan, Xiaohui Zhou, Zhongmin Liu
Pulmonary hypertension (PH) due to left heart disease (LHD) is a common condition associated with significant morbidity. It contributes to the elevation of pulmonary vascular resistance and mean pulmonary pressure, eventually leading to heart failure and even mortality. The present study aimed to explore the potential efficacy of late and long‑term treatment with a Rho‑kinase (ROCK) signaling inhibitor, namely fasudil, in a rat model of end‑stage PH‑LHD. The PH‑LHD model was established by supracoronary aortic banding, and the effect of fasudil treatment on the progression of PH‑LHD was monitored...
June 13, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29888323/circulating-neurotoxic-5-ht2a-receptor-agonist-autoantibodies-in-adult-type-2-diabetes-with-parkinson-s-disease
#15
Mark B Zimering
Aims: To test whether circulating neurotoxic autoantibodies increase in adult type 2 diabetes mellitus with Parkinson's disease (PD) or dementia. To identify the G-protein coupled receptor on neuroblastoma cells mediating neural inhibitory effects in diabetic Parkinson's disease plasma autoantibodies. To determine the mechanism of accelerated neuroblastoma cell death and acute neurite retraction induced by diabetic Parkinson's disease and dementia autoantibodies. Methods: Protein-A eluates from plasma of twelve older adult male diabetic patients having Parkinson's disease (n=10) or dementia (n=2), and eight age-matched control diabetic patients were tested for ability to cause accelerated N2A neuroblastoma cell death and acute neurite retraction...
2018: Journal of Endocrinology and Diabetes
https://www.readbyqxmd.com/read/29885334/compartmentalized-cyclic-nucleotides-have-opposing-effects-on-regulation-of-hypertrophic-phospholipase-c%C3%AE%C2%B5-signaling-in-cardiac-myocytes
#16
Craig A Nash, Loren M Brown, Sundeep Malik, Xiaodong Cheng, Alan V Smrcka
In cardiac myocytes activation of an exchange factor activated by cAMP (Epac) leads to activation of phospholipase Cε (PLCε)-dependent hydrolysis of phosphatidylinositol 4-phosphate (PI4P) in the Golgi apparatus a process critical for development of cardiac hypertrophy. Here we show that β-adrenergic receptor (βAR) stimulation does not stimulate this pathway in the presence of the broad spectrum phosphodiesterase (PDE) inhibitor IBMX, but selective PDE3 inhibition revealed βAR-dependent PI4P depletion...
June 7, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29873936/endothelium-dependent-responses-in-the-microcirculation-observed-in-vivo
#17
REVIEW
W I Rosenblum
Endothelium-dependent responses were first demonstrated 40 years ago in the aorta. Since then, extensive research has been conducted in vitro using conductance vessels and materials derived from them. However, the microcirculation controls blood flow to vital organs and has been the focus of in vivo studies of endothelium-dependent dilation beginning immediately after the first in vitro report. Initial in vivo studies employed a light/dye technique for selectively damaging the endothelium to unequivocally prove, in vivo, the existence of endothelium-dependent dilation and in the microvasculature...
June 6, 2018: Acta Physiologica
https://www.readbyqxmd.com/read/29852493/protecting-podocytes-a-key-target-for-therapy-of-focal-segmental-glomerulosclerosis
#18
Kirk N Campbell, James A Tumlin
BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a histologic pattern of injury demonstrated by renal biopsy that can arise from a diverse range of causes and mechanisms. It has an estimated incidence of 7 per 1 million and is the most common primary glomerular disorder leading to end-stage renal disease in the United States. This review focuses on damage to the podocyte and the consequences of this injury in patients with FSGS, the genetics of FSGS, and approaches to treatment with a focus on the effects on podocytes...
2018: American Journal of Nephrology
https://www.readbyqxmd.com/read/29847776/suppression-of-pax2-attenuates-allodynia-and-hyperalgesia-through-et-1-etar-nfat5-signaling-in-a-rat-model-of-neuropathic-pain
#19
Lydia Wai Tai, Zhiqiang Pan, Liting Sun, Haobo Li, Pan Gu, Stanley Sau Ching Wong, Sookja K Chung, Chi Wai Cheung
Endothelin-1 (ET-1) and its receptors (ETAR/ETBR) emerge to be a key signaling axis in neuropathic pain processing and are recognized as new therapeutic targets. Yet, little is known on the functional regulation of ET-1 axis during neuropathic pain. Bioinformatics analysis indicated that paired box gene 2 (Pax2) or nuclear factor of activated T-cells 5 (NFAT5), two transcription factors involved in the modulation of neurotransmission, may regulate ET-1. Therefore, we hypothesized that ET-1 axis may be regulated by Pax2 or NFAT5 in the development of neuropathic pain...
August 1, 2018: Neuroscience
https://www.readbyqxmd.com/read/29845288/fgf21-attenuates-hypoxia%C3%A2-induced-dysfunction-and-apoptosis-in-hpaecs-through-alleviating-endoplasmic-reticulum-stress
#20
Ali Chen, Jingjing Liu, Jianfeng Zhu, Xuetao Wang, Zhaona Xu, Zhimin Cui, Dan Yao, Zhifeng Huang, Min Xu, Mayun Chen, Peiliang Wu, Manxiang Li, Liangxing Wang, Xiaoying Huang
Vascular endothelial apoptosis and dysfunction have a crucial role in triggering pathological vascular remodeling of hypoxia‑induced pulmonary arterial hypertension (PAH). Fibroblast growth factor (FGF)21, an endocrine regulator, has recently been reported to protect cardiac endothelial cells from damage and suppress inflammatory responses. In addition, FGF21 is reported to be involved in endoplasmic reticulum stress (ERS). Previous studies have suggested that ERS participates in the development of PAH, and attenuation of ERS could be an effective therapeutic strategy for the protection of pulmonary arteries...
May 24, 2018: International Journal of Molecular Medicine
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