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Vascular Pharmacology

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https://www.readbyqxmd.com/read/28192258/binding-and-functional-pharmacological-characteristics-of-gepant-type-antagonists-in-rat-brain-and-mesenteric-arteries
#1
Majid Sheykhzade, Nilofar Amandi, Monica Vidal Pla, Bahareh Abdolalizadeh, Anette Sams, Karin Warfvinge, Lars Edvinsson, Darryl S Pickering
AIM: The neuropeptide calcitonin gene-related peptide (CGRP) is found in afferent sensory nerve fibers innervating the resistance arteries and plays a pivotal role in a number of neurovascular diseases such as migraine and subarachnoid bleedings. The present study investigates the binding and antagonistic characteristics of small non-peptide CGRP receptor antagonists (i.e. gepants) in isolated rat brain and mesenteric resistance arteries. METHODS: The antagonistic behavior of gepants was investigated in isolated rat mesenteric arteries using a wire myograph setup while binding of gepants to CGRP receptors was investigated in rat brain membranes using a radioligand competitive binding assay...
February 10, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28192257/anti-thrombotic-and-pro-fibrinolytic-effects-of-levosimendan-in-human-endothelial-cells-in-vitro
#2
Konstantin A Krychtiuk, Christoph Kaun, Philipp J Hohensinner, Stefan Stojkovic, Jacqueline Seigner, Stefan P Kastl, Andreas Zuckermann, Wolfgang Eppel, Sabine Rauscher, Rainer de Martin, Gerald Maurer, Kurt Huber, Johann Wojta, Walter S Speidl
AIMS: Levosimendan is an inodilator for the treatment of acute decompensated heart failure (HF). Data from clinical studies suggest that levosimendan is particularly effective in HF due to myocardial infarction. After acute revascularization, no reflow-phenomenon is a common complication that may lead to pump failure and cardiogenic shock. Our aim was to examine whether levosimendan interferes with the pro-thrombotic phenotype of activated endothelial cells in vitro. METHODS: Human heart microvascular endothelial cells (HHMEC) and human umbilical vein endothelial cells (HUVEC) were treated with interleukin-1β (IL-1β) (200U/mL) or thrombin (5U/mL) and co-treated with or without levosimendan (0...
February 10, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28188886/propofol-inhibits-high-glucose-induced-pp2a-expression-in-human-umbilical-vein-endothelial-cells
#3
Qichao Wu, Yanjun Zhao, Wenming Duan, Yi Liu, Xiangyuan Chen, Minmin Zhu
Perioperative hyperglycemia is a common clinical metabolic disorder. Hyperglycemia could induce endothelial apoptosis, dysfunction and inflammation, resulting in endothelial injury. Propofol is a widely used anesthetic drug in clinical settings. Our previous studies indicated that propofol, via inhibiting high glucose-induced PP2A expression, attenuated high glucose-induced reactive oxygen species (ROS) accumulation, thus improving endothelial apoptosis, dysfunction and inflammation. However, the mechanisms by which propofol attenuated high glucose-induced PP2A expression is still obscure...
February 8, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28137665/diabetic-microangiopathy-pathogenetic-insights-and-novel-therapeutic-approaches
#4
REVIEW
Rosalinda Madonna, Carmela Rita Balistreri, Yong-Jian Geng, Raffaele De Caterina
Diabetic microangiopathy, including retinopathy, is characterized by abnormal growth and leakage of small blood vessels, resulting in local edema and functional impairment of the depending tissues. Mechanisms leading to the impairment of microcirculation in diabetes are multiple and still largely unclear. However, a dysregulated vascular regeneration appears to play a key role. In addition, oxidative and hyperosmolar stress, as well as the activation of inflammatory pathways triggered by advanced glycation end-products and toll-like receptors, have been recognized as key underlying events...
January 28, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28089842/curbing-tumorigenesis-and-malignant-progression-through-the-pharmacological-control-of-the-wound-healing-process
#5
REVIEW
Melania Dovizio, Angela Sacco, Paola Patrignani
The prevention of cancer development and its progression is an urgent unmet medical need. Novel knowledge on the biology of cancer has evidenced that genetic changes occurring within cancer cells contribute, but are not sufficient, for tumor promotion and progression. The results of clinical studies and experimental animal models have suggested pursuing new avenues for the prevention of cancer development in the early stages, by using drugs that modulate platelet responses and those interfering with the synthesis and action of the mediators of inflammation...
January 12, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28087358/vascular-calcification-abrogates-the-nicorandil-mediated-cardio-protection-in-ischemia-reperfusion-injury-of-rat-heart
#6
Sriram Ravindran, Jeyashri Murali, Sunil Kumar Amirthalingam, Senthilkumar Gopalakrishnan, Gino A Kurian
The present study was aimed to determine the efficacy of nicorandil in treating cardiac reperfusion injury with an underlying co-morbidity of vascular calcification (VC). Adenine diet was used to induce VC in Wistar rat and the heart was isolated to induce global ischemia reperfusion (IR) by Langendorff method, with and without the nicorandil (7.5mg/kg) pre-treatment and compared with those fed on normal diet. The adenine-treated rats displayed abnormal ECG changes and altered mitochondrial integrity compared to a normal rat heart...
January 10, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28082117/targeting-endothelial-metabolism-for-anti-angiogenesis-therapy-a-pharmacological-perspective
#7
REVIEW
Rindert Missiaen, Francisco Morales-Rodriguez, Guy Eelen, Peter Carmeliet
Current anti-angiogenic therapies in malignant and ocular diseases target growth factor signaling in order to attenuate excessive vascular growth. Although initial responses are promising, overall therapeutic success is limited due to insufficient efficiency, tumor refractoriness and resistance. Emerging evidence suggests that diverse growth factor signaling pathways in endothelial cells (ECs) converge onto cellular metabolism, creating an attractive target for novel alternative anti-angiogenic therapies. Recent studies show that ECs rely on glycolysis for ATP and biomass synthesis, necessary for proliferation and migration, key processes of angiogenesis...
January 7, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28069546/g004-a-synthetic-sulfonylurea-compound-exerts-anti-atherosclerosis-effects-by-targeting-sirt1-in-apoe-mice
#8
Lifen Qian, Lingman Ma, Guanzhong Wu, Qian Yu, Huisheng Lin, Qidi Ying, Dan Wen, Cong Gao
Atherosclerosis attracts increasing global attention because of its morbidity and mortality. G004, as a synthetic sulfonylurea compound, has been confirmed to have anti-hyperglycaemia, anti-platelet and anti-thrombus effects. The aim of the present study was to investigate whether G004 suppress the onset and development of atherosclerosis and illuminate its probable mechanism of action. ApoE(-/-) mice that were fed a high-fat diet were randomly divided into five groups by weight; subsequently, they were treated with vehicle, G004, at different doses or atorvastatin once daily for 12weeks...
January 6, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28064014/gpr55-agonist-lysophosphatidylinositol-and-lysophosphatidylcholine-inhibit-endothelial-cell-hyperpolarization-via-gpr-independent-suppression-of-na-ca-2-exchanger-and-endoplasmic-reticulum-ca-2-refilling
#9
Alexander I Bondarenko, Fabrizio Montecucco, Olga Panasiuk, Vadim Sagach, Nataliya Sidoryak, Karim J Brandt, François Mach
Lysophosphatidylinositol (LPI) and lysophosphatidylcholine (LPC) are lipid signaling molecules that induce endothelium-dependent vasodilation. In addition, LPC suppresses acetylcholine (Ach)-induced responses. We aimed to determine the influence of LPC and LPI on hyperpolarizing responses in vitro and in situ endothelial cells (EC) and identify the underlying mechanisms. Using patch-clamp method, we show that LPI and LPC inhibit EC hyperpolarization to histamine and suppress Na(+)/Ca(2+) exchanged (NCX) currents in a concentration-dependent manner...
January 5, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/27993686/microrna-126-suppresses-inflammation-in-endothelial-cells-under-hyperglycemic-condition-by-targeting-hmgb1
#10
Song-Tao Tang, Feng Wang, Min Shao, Yuan Wang, Hua-Qing Zhu
MicroRNA-126(miR-126) targets involved in inflammation need to be identified. In this study, we aim to investigate whether high-mobility group box 1(HMGB1), an inflammation-related gene, is the target of miR-126 in diabetic vascular endothelium. The diabetic apoE(-/-) mice model, a classical diabetic atherosclerosis model, was established. The aorta of diabetic apoE(-/-) mice showed decrease of miR-126 and elevation of HMGB1 and inflammation. Next, we employed several in vitro experiments to address the role of miRNA-126 on the regulation of HMGB1 in endothelial cells under hyperglycemic and inflammatory conditions...
December 18, 2016: Vascular Pharmacology
https://www.readbyqxmd.com/read/27932069/quercetin-attenuates-vascular-calcification-by-inhibiting-oxidative-stress-and-mitochondrial-fission
#11
Lei Cui, Zhong Li, Xueying Chang, Guangting Cong, Lirong Hao
Vascular calcification is a strong independent predictor of increased cardiovascular morbidity and mortality and has a high prevalence among patients with chronic kidney disease. The present study investigated the effects of quercetin on vascular calcification caused by oxidative stress and abnormal mitochondrial dynamics both in vitro and in vivo. Calcifying vascular smooth muscle cells (VSMCs) treated with inorganic phosphate (Pi) exhibited mitochondrial dysfunction, as demonstrated by decreased mitochondrial potential and ATP production...
December 5, 2016: Vascular Pharmacology
https://www.readbyqxmd.com/read/27993685/simvastatin-inhibits-homocysteine-induced-crp-generation-via-interfering-with-the-ros-p38-erk1-2-signal-pathway-in-rat-vascular-smooth-muscle-cells
#12
Xiaoming Pang, Jigang Si, Shouzhu Xu, Yuxia Li, Juntian Liu
Inflammation plays a pivotal role throughout the formation and progression of atherosclerosis. As the most representative inflammatory marker, C-reactive protein (CRP) directly participates in the initiation and development of atherosclerosis. The elevated homocysteine (Hcy) level in plasma is an independent risk factor for atherosclerosis. We previously reported that Hcy produces a pro-inflammatory effect by stimulating CRP expression in vascular smooth muscle cells (VSMCs). The present study observed the effect of simvastatin on Hcy-induced CRP expression in VSMCs and the molecular mechanisms...
January 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/27890480/chemerin-induced-arterial-contraction-is-gi-and-calcium-dependent
#13
David J Ferland, Emma S Darios, Richard R Neubig, Benita Sjögren, Nguyen Truong, Rosa Torres, Thomas S Dexheimer, Janice M Thompson, Stephanie W Watts
Chemerin is an adipokine associated with increased blood pressure, and may link obesity with hypertension. We tested the hypothesis that chemerin-induced contraction of the vasculature occurs via calcium flux in smooth muscle cells. Isometric contraction of rat aortic rings was performed in parallel with calcium kinetics of rat aortic smooth muscle cells to assess the possible signaling pathway. Chemerin-9 (nonapeptide of the chemerin S(157) isoform) caused a concentration-dependent contraction of isolated aorta (EC50 100nM) and elicited a concentration-dependent intracellular calcium response (EC50 10nM)...
January 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/26239884/methylthiouracil-a-new-treatment-option-for-sepsis
#14
Soyoung Kwak, Sae-Kwang Ku, Hyejin Kang, Moon-Chang Baek, Jong-Sup Bae
The screening of bioactive compound libraries can be an effective approach for repositioning FDA-approved drugs or discovering new treatments for human diseases. Inhibition of high mobility group box 1 (HMGB1) and restoration of endothelial integrity are emerging as an attractive therapeutic strategies in the management of severe sepsis or septic shock. Here, we examined the effects of methylthiouracil (MTU), used as antithyroid drug, by monitoring the effects on lipopolysaccharide (LPS)- or cecal ligation and puncture (CLP)-mediated release of HMGB1, and on the modulation of HMGB1-mediated inflammatory responses...
January 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/27884760/marine-n-3-fatty-acids-and-the-risk-of-new-onset-postoperative-atrial-fibrillation-after-cardiac-surgery
#15
REVIEW
Pia T Dinesen, Erik B Schmidt
No abstract text is available yet for this article.
December 2016: Vascular Pharmacology
https://www.readbyqxmd.com/read/27871853/nur77-downregulation-triggers-pulmonary-artery-smooth-muscle-cell-proliferation-and-migration-in-mice-with-hypoxic-pulmonary-hypertension-via-the-axin2-%C3%AE-catenin-signaling-pathway
#16
Xiaowei Nie, Jianxin Tan, Youai Dai, Wenjun Mao, Yuan Chen, Guowei Qin, Guirong Li, Chenyou Shen, Jingjing Zhao, Jingyu Chen
Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by remodeling of the pulmonary vasculature, including marked proliferation and reduced apoptosis of pulmonary artery smooth muscle cells (PASMCs). Members of the nuclear receptor 4A (NR4A) subfamily are involved in a variety of biological events, such as cell apoptosis, proliferation, inflammation, and metabolism. Activation of Nur77 (an orphan nuclear receptor that belongs to NR4A subfamily) has recently been reported to be as a beneficial agent in the treatment of cardiovascular and metabolic diseases...
December 2016: Vascular Pharmacology
https://www.readbyqxmd.com/read/27867031/marine-n-3-fatty-acids-are-incorporated-into-atrial-tissue-but-do-not-correlate-with-postoperative-atrial-fibrillation-in-cardiac-surgery
#17
J Gu, Søren Lundbye-Christensen, Rikke B Eschen, Annette Andreasen, Jan J Andreasen
OBJECTIVES: Postoperative new-onset atrial fibrillation (POAF) in cardiac surgery is associated with increased morbidity and mortality. Because n-3 polyunsaturated fatty acids (n-3 PUFA) have an antiarrhythmic effect, we hypothesized that a high content of marine n-3 PUFA in the atrial wall was associated with a reduced risk of POAF. DESIGN: Venous blood and tissue from the right atrial appendage were obtained from 50 patients undergoing elective cardiac surgery...
December 2016: Vascular Pharmacology
https://www.readbyqxmd.com/read/27865826/heavy-menstrual-bleeding-in-women-treated-with-rivaroxaban-and-vitamin-k-antagonists-and-the-risk-of-recurrent-venous-thromboembolism
#18
Agata Hanna Bryk, Magdalena Piróg, Krzysztof Plens, Anetta Undas
Anticoagulants increase the risk of heavy menstrual bleeding (HMB). We sought to investigate the incidence, predictors and management of HMB in women on rivaroxaban compared to those on vitamin K antagonists (VKA). We addressed the issue as to whether HMB is associated with VTE recurrences. We performed a single-center prospective study in menstruating women aged 18-55years treated with rivaroxaban or VKA≥3months since the index VTE episode. Seventy six women on rivaroxaban and 45 patients on VKA were included...
December 2016: Vascular Pharmacology
https://www.readbyqxmd.com/read/27826031/tlr-signalling-and-association-of-tlr-polymorphism-with-cardiovascular-diseases
#19
REVIEW
Swati Sharma, Iti Garg, Mohammad Z Ashraf
Toll-Like receptors (TLRs) are the primary receptors of innate immunity. Considerable evidences have shown that innate immune defence interaction with pro-inflammatory pathways could be through TLRs that in turn leads to development of inflammatory diseases. These TLRs are present on various tissues and cells of cardiovascular system. Previous studies involving SNPs analysis of TLRs demonstrated that TLRs are involved in development and progression of diseases like atherosclerosis, cardiac dysfunction in sepsis and congestive heart failure...
December 2016: Vascular Pharmacology
https://www.readbyqxmd.com/read/27825869/transendothelial-glucose-transport-is-not-restricted-by-extracellular-hyperglycaemia
#20
Sarka Tumova, Asimina Kerimi, Karen E Porter, Gary Williamson
Endothelial cells are routinely exposed to elevated glucose concentrations post-prandially in healthy individuals and permanently in patients with metabolic syndrome and diabetes, and so we assessed their sugar transport capabilities in response to high glucose. In human umbilical vein (HUVEC), saphenous vein, microdermal vessels and aorta, GLUT1 (SLC2A1), GLUT3 (SLC2A3), GLUT6 (SLC2A6), and in microdermal vessels also GLUT12 (SLC2A12), were the main glucose transporters as assessed by mRNA, with no fructose transporters nor SGLT1 (SLC5A1)...
December 2016: Vascular Pharmacology
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