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Endothelin-1

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https://www.readbyqxmd.com/read/28732172/role-of-endothelin-1-and-its-receptors-eta-and-etb-in-the-survival-of-human-vascular-endothelial-cells
#1
Marianne Mikhail, Pierre H Vachon, Pedro D'Orleans-Juste, Danielle Jacques, Ghassan Bkaily
Our previous work showed the presence of endothelin-1 (ET-1) receptors, ETA and ETB, in human vascular endothelial cells (hVECs). In this study, we wanted to verify whether ET-1 via the activation of its receptors ETA and/or ETB (ETAR and ETBR respectively) play a role in the survival of hVECs. Our results showed that treatment of hVECs with ET-1 prevented apoptosis induced by genistein, an effect that was mimicked by treatment with ETBR specific agonist IRL1620. Furthermore, blockade of ETBR with the selective ETBR antagonist A192621 prevented the anti-apoptotic effect of ET-1 in hVECs...
July 21, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28731190/lutein-protects-against-severe-traumatic-brain-injury-through-anti%C3%A2-inflammation-and-antioxidative-effects-via-icam%C3%A2-1-nrf%C3%A2-2
#2
Dianhui Tan, Xiaoping Yu, Moran Chen, Junchen Chen, Jincheng Xu
Many studies have reported that lutein may exert its biological activities, including anti‑inflammation, anti‑oxidase and anti‑apoptosis, through effects on reactive oxygen species (ROS). Thus, lutein may prevent the damaging activities of ROS in cells. The current study investigated the effect of lutein against severe traumatic brain injury (STBI) and examined the mechanism of this protective effect. Sprague‑Dawley rats were randomly divided into 5 groups: Control group, STBI model group, 40 mg/kg lutein‑treated group, 80 mg/kg lutein‑treated group and 160 mg/kg lutein‑treated group...
July 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28729555/inhibition-of-phosphodiesterase-5-suppresses-calcineurin-nfat-mediated-trpc6-expression-in-pulmonary-artery-smooth-muscle-cells
#3
Shaojun Li, Yilin Pan, Rui Ke, Xinming Xie, Cui Zhai, Wenhua Shi, Jian Wang, Xin Yan, Limin Chai, Qingting Wang, Qianqian Zhang, Xiaofan Su, Lan Yang, Li Gao, Manxiang Li
The up-regulation of transient receptor potential channel 6 (TRPC6) has been found to contribute to the proliferation of pulmonary artery smooth muscle cells (PASMCs), and inhibition of phosphodiesterase-5 (PDE5) has been shown to suppress TRPC6 expression in PASMCs. However, the molecular mechanisms underlying the up-regulation of TRPC6 expression and PDE5 modulation of TRPC6 expression in PASMCs remain largely unclear. The aim of this study is to address these issues. Endothelin-1 (ET-1) dose and time-dependently up-regulated TRPC6 expression in primary cultured rat PASMCs, and this was accompanied with the activation of calcineurin and subsequent translocation of NFATc4 to the nucleus...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729387/leg-blood-flow-is-impaired-during-small-muscle-mass-exercise-in-copd-patients
#4
Ulrik Winning Iepsen, Gregers Druedal Wibe Munch, Mette Rugbjerg, Camilla Koch Ryrsø, Niels Secher, Ylva Hellsten, Peter Lange, Bente Klarlund Pedersen, Pia Thaning, Stefan P Mortensen
Skeletal muscle blood flow is regulated to match the oxygen demand and dysregulation could contribute to exercise intolerance in patients with COPD. We measured leg hemodynamics and metabolites from vasoactive compounds in muscle interstitial fluid and plasma at rest, during one-legged knee-extensor exercise, and during arterial infusions of sodium nitroprusside (SNP) and acetylcholine (ACh), respectively. Ten patients with moderate to severe COPD and eight age- and sex matched healthy controls were studied...
July 20, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28726796/three-year-change-in-endothelin-1-and-markers-of-vascular-remodelling-in-a-bi-ethnic-south-african-cohort-the-sabpa-study
#5
C S du Plooy, C M C Mels, H W Huisman, R Kruger
South Africans are at high risk for developing cardiovascular disease. Endothelin-1 is known for its vasoconstrictive properties and its ability to contribute to vascular structural changes. In this study we investigated the association of change in endothelin-1 levels and change in markers implicated in vascular remodelling after 3 years. Serum endothelin-1 levels and markers of vascular remodelling such as carotid intima-media thickness, carotid cross-sectional wall area (CSWA) and arterial compliance were measured...
July 20, 2017: Journal of Human Hypertension
https://www.readbyqxmd.com/read/28726655/influence-of-beta-blockers-and-ivabradine-on-long-term-prognosis-of-patients-with-stable-angina
#6
T Ilashchuk, O Glubochenko, B Senyuk, N Bachuk-Ponich, I Lukashevich
The purpose of the study was to evaluate the influence of beta-blockers and ivabradine on long-term prognosis of patients with stable angina. 90 patients with stable angina that have been involved in present study along with nitrates, antiplatelet agents and statins received bisoprolol (Group I), carvedilol (Group II) and ivabradine (Group III). We analyzed the following indicators: patient adherence to treatment, cases of myocardial infarction and circulatory decompensation, which resulted in necessity of patient's hospitalization during the year of observation, calculating the probability of achieving a key prognostic endpoint by patient using the concept of the odds ratio and determination of important components in the progression of the disease...
June 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28720331/a-novel-antihypertension-agent-sargachromenol-d-from-marine-brown-algae-sargassum-siliquastrum-exerts-dual-action-as-an-l-type-ca-2-channel-blocker-and-endothelin-a-b2-receptor-antagonist
#7
Byong-Gon Park, Woon-Seob Shin, Sangtae Oh, Gab-Man Park, Nam Ik Kim, Seokjoon Lee
We isolated the novel vasoactive marine natural products, (5E,10E)-14-hydroxy-2,6,10-trimethylpentadeca-5,10-dien-4-one (4) and sargachromenol D (5), from Sargassum siliquastrum collected from the coast of the East Sea in South Korea by using activity-guided HPLC purification. The compounds effectively dilated depolarization (50mMK(+))-induced basilar artery contraction with EC50 values of 3.52±0.42 and 1.62±0.63μM, respectively, but only sargachromenol D (5) showed a vasodilatory effect on endothelin-1 (ET-1)-induced basilar artery contraction (EC50=9...
July 6, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28716993/low-soluble-fms-like-tyrosine-kinase-1-endoglin-and-endothelin-1-levels-in-women-with-confirmed-or-suspected-preeclampsia-using-proton-pump-inhibitors
#8
Langeza Saleh, Raaho Samantar, Ingrid M Garrelds, Anton H van den Meiracker, Willy Visser, A H Jan Danser
Patients with preeclampsia display elevated placenta-derived sFlt-1 (soluble Fms-like tyrosine kinase-1) and endoglin levels and decreased placental growth factor levels. Proton pump inhibitors (PPIs) decrease trophoblast sFlt-1 and endoglin secretion in vitro. PPIs are used during pregnancy to combat reflux disease. Here, we investigated whether PPIs affect sFlt-1 in women with confirmed/suspected preeclampsia, making use of a prospective cohort study involving 430 women. Of these women, 40 took PPIs (6 esomeprazole, 32 omeprazole, and 2 pantoprazole) for 8 to 45 (median 29) days before sFlt-1 measurement...
July 17, 2017: Hypertension
https://www.readbyqxmd.com/read/28715643/new-insights-into-the-non-hemostatic-role-of-von-willebrand-factor-in-endothelial-protection
#9
Silvia Agostini, Vincenzo Lionetti
During exposure to ischemia and reperfusion (I/R) insult, angiotensin II (AngII)-induced endothelin-1 (ET-1) upregulation in endothelial cells progressively impairs nitric oxide (NO) bioavailability while increasing levels of superoxide anion (O2-) and leading to the onset of endothelial dysfunction. Moreover, the overexpression of ET-1 increases the endothelial and circulating levels of von Willebrand Factor (vWF), a glycoprotein with a crucial role in arterial thrombus formation. Nowadays, the non-hemostatic role of endothelial vWF is emerging; although we not yet know if its increased expression is cause or consequence of endothelial dysfunction...
July 17, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28713482/comparative-therapeutic-effects-of-minocycline-treatment-and-bone-marrow-mononuclear-cell-transplantation-following-striatal-stroke
#10
Celice C Souza, Michelle Castro da Silva, Rosana Telma Lopes, Marcelo M Cardoso, Lucas Lacerda de Souza, Adriano Guimarães Santos, Ijair Rogério Dos Santos, Edna C S Franco, Walace Gomes-Leal
We explored the comparative effects of minocycline treatment and intrastriatal BMMC transplantation after experimental striatal stroke in adult rats. Male Wistar adult rats were divided as follows: saline-treated (N = 5), minocycline-treated (N = 5), and BMMC-transplanted (N = 5) animals. Animals received intrastriatal microinjections of 80 pmol of endothelin-1 (ET-1). Behavioral tests were performed at 1, 3, and 7 days postischemia. Animals were treated with minocycline (50 mg/kg, i.p.) or intrastriatal transplants of 106 BMMCs at 24 h postischemia...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28713274/stimulation-of-adenosine-a2b-receptor-inhibits-endothelin-1-induced-cardiac-fibroblast-proliferation-and-%C3%AE-smooth-muscle-actin-synthesis-through-the-camp-epac-pi3k-akt-signaling-pathway
#11
Sarawuth Phosri, Ajaree Arieyawong, Kwanchai Bunrukchai, Warisara Parichatikanond, Akiyuki Nishimura, Motohiro Nishida, Supachoke Mangmool
Background and Purpose: Cardiac fibrosis is characterized by an increase in fibroblast proliferation, overproduction of extracellular matrix proteins, and the formation of myofibroblast that express α-smooth muscle actin (α-SMA). Endothelin-1 (ET-1) is involved in the pathogenesis of cardiac fibrosis. Overstimulation of endothelin receptors induced cell proliferation, collagen synthesis, and α-SMA expression in cardiac fibroblasts. Although adenosine was shown to have cardioprotective effects, the molecular mechanisms by which adenosine A2 receptor inhibit ET-1-induced fibroblast proliferation and α-SMA expression in cardiac fibroblasts are not clearly identified...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28712433/two-year-prognosis-after-acute-coronary-syndrome-in-younger-patients-association-with-feeling-depressed-in-the-prior-year-and-bdi-ii-score-and-endothelin-1
#12
Luba Yammine, Lorraine Frazier, Nikhil S Padhye, Jennifer E Sanner, Matthew M Burg
OBJECTIVE: To examine the effects of depressive symptoms and Endothelin (ET)-1 on 2-year prognosis in younger patients with acute coronary syndrome (ACS). Depression is associated with poor post-ACS prognosis; however, few investigations have focused on younger patients. Importantly, the studies that did emphasize younger patients suggested that the influence of depression on prognosis could be more robust in younger subgroups. The particular links between depression and poor prognosis in younger patients have yet to be definitively determined...
August 2017: Journal of Psychosomatic Research
https://www.readbyqxmd.com/read/28708138/blocking-endothelin-1-receptor-%C3%AE-catenin-circuit-sensitizes-to-chemotherapy-in-colorectal-cancer
#13
Roberta Cianfrocca, Laura Rosanò, Piera Tocci, Rosanna Sestito, Valentina Caprara, Valeriana Di Castro, Ruggero De Maria, Anna Bagnato
The limited clinical response to conventional chemotherapeutics observed in colorectal cancer (CRC) may be related to the connections between the hyperactivated β-catenin signaling and other pathways in CRC stem-like cells (CRC-SC). Here, we show the mechanistic link between the endothelin-1 (ET-1)/ET-1 receptor (ET-1R) signaling and β-catenin pathway through the specific interaction with the signal transducer β-arrestin1 (β-arr1), which initiates signaling cascades as part of the signaling complex. Using a panel of patient-derived CRC-SC, we show that these cells secrete ET-1 and express ETAR and β-arr1, and that the activation of ETAR/β-arr1 axis promotes the cross-talk with β-catenin signaling to sustain stemness, epithelial-to-mesenchymal transition (EMT) phenotype and response to chemotherapy...
July 14, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28705795/selective-deletion-of-leptin-signaling-in-endothelial-cells-enhances-neointima-formation-and-phenocopies-the-vascular-effects-of-diet-induced-obesity-in-mice
#14
Astrid Hubert, Magdalena L Bochenek, Eva Schütz, Rajinikanth Gogiraju, Thomas Münzel, Katrin Schäfer
OBJECTIVE: Obesity is associated with elevated circulating leptin levels and hypothalamic leptin resistance. Leptin receptors (LepRs) are expressed on endothelial cells, and leptin promotes neointima formation in a receptor-dependent manner. Our aim was to examine the importance of endothelial LepR (End.LepR) signaling during vascular remodeling and to determine whether the cardiovascular consequences of obesity are because of hyperleptinemia or endothelial leptin resistance. APPROACH AND RESULTS: Mice with loxP-flanked LepR alleles were mated with mice expressing Cre recombinase controlled by the inducible endothelial receptor tyrosine kinase promoter...
July 13, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28704616/inhibition-of-platelet-aggregation-ex-vivo-is-repressed-in-apolipoprotein-e-deficient-mice
#15
Emilie Carrier, Martin Houde, Michel Grandbois, Ghassan Bkaily, Timothy D Warner, Pedro D'Orleans-Juste
In the present study, we assessed if the endogenous platelet inhibitory mechanisms are altered in the early to moderate stages of the atherosclerotic process. Apolipoprotein E deficient mice (ApoE-/-), a mouse model of atherosclerosis, and their wild-type (WT) counterparts were used to assess agonist-stimulated synthesis of prostacyclin (PGI2), inhibition of platelet aggregation ex vivo and intra-platelet cAMP levels. Basal U46619 and ADP -induced platelet aggregation in vitro were increased in ApoE-/- mice at 18-20 weeks in comparison to 8 10 weeks of age...
July 13, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28701603/is-endothelin-gene-polymorphism-associated-with-postoperative-atrial-fibrillation-in-patients-undergoing-coronary-artery-bypass-grafting
#16
Ira Dhawan, Minati Choudhury, Milind P Hote, Anushree Gupta, Poonam Malhotra, Kalaivani V Mani
BACKGROUND: The mechanism of development of atrial fibrillation (AF) in patients undergoing coronary artery bypass grafting (CABG) has not been clearly defined, and the involvement of multiple factors such as advanced age, withdrawal of β-blockers, inadequate atrial protection, and electrolyte imbalance, particularly hypomagnesemia has been documented by several authors. Despite all the available pharmacologic prophylaxis, incidence of AF still remains high in this group of patients...
July 2017: Annals of Cardiac Anaesthesia
https://www.readbyqxmd.com/read/28701323/renal-denervation-attenuates-hypertension-but-not-salt-sensitivity-in-etb-receptor-deficient-rats
#17
Bryan K Becker, Amanda C Feagans, Daian Chen, Malgorzata Kasztan, Chunhua Jin, Joshua S Speed, Jennifer S Pollock, David M Pollock
Hypertension is a prevalent pathology that increases risk for numerous cardiovascular diseases. Because the etiology of hypertension varies across patients, specific and effective therapeutic approaches are needed. The role of renal sympathetic nerves is established in numerous forms of hypertension, but their contribution to salt-sensitivity and interaction with factors such as endothelin-1 are poorly understood. Rats deficient of functional ETB receptors (ETB-def) on all tissues except sympathetic nerves are hypertensive and exhibit salt-sensitive increases in blood pressure...
July 12, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28698270/association-between-endothelin-1-levels-and-kidney-disease-among-blacks
#18
Casey M Rebholz, Jane L Harman, Morgan E Grams, Adolfo Correa, Daichi Shimbo, Josef Coresh, Bessie A Young
Endothelin-1, a marker of endothelial dysfunction, is a potent vasoconstrictor released by endothelial cells and an important regulator of renal physiology. It is not known whether elevated serum levels of endothelin-1 indicate future risk of kidney disease in the general population. In participants in the Jackson Heart Study, a community-based observational study of cardiovascular risk in black adults, we measured serum endothelin-1 level at baseline (2000-2004; n=3538). We defined incident CKD as eGFR<60 ml/min per 1...
July 11, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28696251/endothelin-1-stimulates-vasoconstriction-through-rab11a-serine-177-phosphorylation
#19
Xue Zhai, Marie D Leo, Jonathan H Jaggar
Rationale: Large-conductance calcium (Ca(2+))-activated potassium channels (BK) are composed of pore-forming BKα and auxiliary β1 subunits in arterial smooth muscle cells (myocytes). Vasoconstrictors, including endothelin-1 (ET-1), inhibit myocyte BK channels, leading to contraction, but mechanisms involved are unclear. Recent evidence indicates that BKα is primarily plasma membrane-localized, whereas the cellular location of β1 can be rapidly altered by Rab11A-positive recycling endosomes. Whether vasoconstrictors regulate the multi-subunit composition of surface BK channels to stimulate contraction is unclear...
July 10, 2017: Circulation Research
https://www.readbyqxmd.com/read/28694457/characterisation-of-preproendothelin-1-derived-peptides-identifies-endothelin-like-domain-peptide-as-a-modulator-of-endothelin-1
#20
Jale Yuzugulen, Julie A Douthwaite, Elizabeth G Wood, Inmaculada C Villar, Nimesh S A Patel, James Jegard, Hubert Gaertner, Irène Rossitto-Borlat, Keith Rose, Oliver Hartley, Pedro R Cutillas, Amrita Ahluwalia, Roger Corder
Endothelin-1 (ET-1) is involved in the pathogenesis of cardiac and renal diseases, and in the progression of tumour growth in cancer, but current diagnosis and treatment remain inadequate. Peptides derived from the 212 amino acid precursor preproendothelin-1 (ppET-1) may have utility as biomarkers, or cause biological effects that are unaffected by endothelin receptor antagonists. Here, we used specific immunoassays and LC-MS/MS to identify NT-proET-1 (ppET-1[18-50]), Endothelin-Like Domain Peptide (ELDP, ppET-1[93-166]) and CT-proET-1 (ppET-1[169-212]) in conditioned media from cultured endothelial cells...
July 10, 2017: Scientific Reports
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