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Vascular pharmacology

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https://www.readbyqxmd.com/read/29785139/blockage-of-store-operated-ca-2-entry-antagonizes-epstein-barr-virus-promoted-angiogenesis-by-inhibiting-ca-2-signaling-regulated-vegf-production-in-nasopharyngeal-carcinoma
#1
Jiaxiang Ye, Junqi Huang, Qian He, Weilin Zhao, Xiaoying Zhou, Zhe Zhang, Yongqiang Li, Jiazhang Wei, Jinyan Zhang
Background: Epstein-Barr virus (EBV) actively contributes to the pathological process of nasopharyngeal carcinoma (NPC) by enabling NPC cells to acquire various capacities required for their malignant biological actions. Our earlier works demonstrated that EBV-encoded latent membrane protein 1 (LMP1) enhanced vascular endothelial growth factor (VEGF)-mediated angiogenesis by boosting store-operated Ca2+ entry (SOCE) upon extracellular epidermal growth factor (EGF) stimulation. However, the antagonistic effects of SOCE blockage on EBV-promoted angiogenesis must be appropriately evaluated in vivo, and the global effect of EBV infection on the EGF-elicited cytosolic Ca2+ signaling, which regulates VEGF-mediated angiogenesis remains to be further clarified...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/29785049/involvement-of-inhibitor-kappa-b-kinase-2-ikk2-in-the-regulation-of-vascular-tone
#2
Youngin Kwon, Soo-Kyoung Choi, Seonhee Byeon, Young-Ho Lee
Inhibitor kappa B kinase 2 (IKK2) plays an essential role in the activation of nuclear factor kappa B (NF-kB). Recently, it has been suggested that IKK2 acts as a myosin light chain kinase (MLCK) and contributes to vasoconstriction in mouse aorta. However, the underlying mechanisms are still unknown. Therefore, we investigated whether IKK2 acts as a MLCK or regulates the activity of myosin light chain phosphatase (MLCP). Pressure myograph was used to measure vascular tone in rat mesenteric arteries. Immunofluorescence staining was performed to identify phosphorylation levels of MLC (ser19), MYPT1 (thr853 and thr696) and CPI-17 (thr38)...
May 21, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29782549/sphingosine-1-phosphate-receptor-2-facilitates-pulmonary-fibrosis-through-potentiating-il-13-pathway-in-macrophages
#3
Juanjuan Zhao, Yasuo Okamoto, Yuya Asano, Kazuhiro Ishimaru, Sho Aki, Kazuaki Yoshioka, Noriko Takuwa, Takashi Wada, Yutaka Inagaki, Chiaki Takahashi, Takumi Nishiuchi, Yoh Takuwa
Idiopathic pulmonary fibrosis is a devastating disease with poor prognosis. The pathogenic role of the lysophospholipid mediator sphingosine-1-phosphate and its receptor S1PR2 in lung fibrosis is unknown. We show here that genetic deletion of S1pr2 strikingly attenuated lung fibrosis induced by repeated injections of bleomycin in mice. We observed by using S1pr2LacZ/+ mice that S1PR2 was expressed in alveolar macrophages, vascular endothelial cells and alveolar epithelial cells in the lung and that S1PR2-expressing cells accumulated in the fibrotic legions...
2018: PloS One
https://www.readbyqxmd.com/read/29780806/myeloperoxidase-negatively-regulates-neutrophil-endothelial-cell-interactions-by-impairing-%C3%AE-m%C3%AE-2-integrin-function-in-sterile-inflammation
#4
Alan Tseng, Kyungho Kim, Jing Li, Jaehyung Cho
Interactions of neutrophils with endothelial cells (ECs) and platelets contribute to tissue damage and vascular occlusion under sterile inflammatory conditions. However, the molecular mechanisms regulating the cell-cell interactions remain poorly understood. Previous studies suggest that reactive oxygen species, such as hydrogen peroxide (H2 O2 ), produced from NADPH oxidase 2 play a critical role in platelet-neutrophil interactions by regulating the function of neutrophil αMβ2 integrin during sterile inflammation...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29777848/effects-on-mortality-and-cardiovascular-events-of-adherence-to-guideline-recommended-therapy-4-years-after-lower-extremity-arterial-revascularization
#5
M Thiney, N Della Schiava, R Ecochard, P Feugier, P Lermusiaux, A Millon, A Long
OBJECTIVES: All patients with lower extremity peripheral arterial disease (LE-PAD) should benefit from recommended pharmacologic therapies including antiplatelet agents, angiotensin converting enzyme inhibitors (ACE) or Angiotensin receptor blockers (ARB), and HMG-CoA-reductase inhibitors (statins). In the present study, this triple therapy was defined as the best medical treatment. This study was designed to determine the current risk for cardiovascular (CV) events and mortality and also to evaluate the effect of pharmacologic treatment on patient's survival, CV events and additional vascular surgery in vascularized LE-PAD patients...
May 16, 2018: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/29764601/adolescent-habitual-caffeine-consumption-and-hemodynamic-reactivity-during-rest-psychosocial-stress-and-recovery
#6
Jack E James, Birna Baldursdottir, Kamilla R Johannsdottir, Heiddis B Valdimarsdottir, Inga Dora Sigfusdottir
OBJECTIVE: Most adolescents regularly consume caffeine. Whereas observational studies have suggested that coffee may be cardio-protective, pharmacological experimentation with adults shows that caffeine at dietary doses increases blood pressure, thereby implicating regular caffeine consumption as a potential source of harm for cardiovascular health. The present study was in response to the dearth of caffeine research among younger consumers. It was hypothesised that compared to the consumption of little or no caffeine, adolescents who habitually consume caffeine have overall higher blood pressure and increased vascular resistance...
July 2018: Journal of Psychosomatic Research
https://www.readbyqxmd.com/read/29763440/endothelium-targeted-delivery-of-dexamethasone-by-anti-vcam-1-saint-o-somes-in-mouse-endotoxemia
#7
Ranran Li, Piotr S Kowalski, Henriëtte W M Morselt, Ilona Schepel, Rianne M Jongman, Adnan Aslan, Marcel H J Ruiters, Jan G Zijlstra, Grietje Molema, Matijs van Meurs, Jan A A M Kamps
Microvascular endothelial cells play a pivotal role in the pathogenesis of sepsis-induced inflammatory responses and multiple organ failure. Therefore, they represent an important target for pharmacological intervention in the treatment of sepsis. Glucocorticosteroids were widely used in the treatment of sepsis but vast evidence to support their systemic use is lacking. The limited effects of glucocorticoids in the treatment of sepsis may be explained by differential effects of drug initiated NF-κB inhibition in different cell types and insufficient drug delivery in target cells...
2018: PloS One
https://www.readbyqxmd.com/read/29762881/colchicine-a-microtubule-disassembling-drug-in-the-therapy-of-cardiovascular-diseases
#8
George N Chaldakov
Colchicum autumnale, from which colchicine has been isolated more than 100 years ago, has been used as a treatment for pain and swelling for thousands of years. It is one of the few drugs known from that time period whose use has survived to modernity. Over the past decades, advances in the knowledge of (i) cytoskeletal microtubules (МТ), and (ii) anti-inflammatory and anti-fibrotic effects of colchicine, a classical MT-disassembling (tubulin-targeting) agent, have led to potential new uses for this very old drug extended beyond acute gouty arthritis and familial Mediterranean fever...
May 15, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29760727/expanded-cd133-cells-from-human-umbilical-cord-blood-improved-heart-function-in-rats-after-severe-myocardial-infarction
#9
Alejandro Correa, Gabriel Salles Ottoboni, Alexandra Cristina Senegaglia, Luiz Guilherme Achcar Capriglione, Nelson Itiro Miyague, Lidiane Maria Boldrini Leite, Valderez Ravaglio Jamur, Carmen Lúcia Kuniyoshi Rebelatto, Márcia Olandoski, Paulo Roberto Slud Brofman
Pharmacological approaches are partially effective in limiting infarct size. Cell therapies using a cell population enriched with endothelial progenitor cells (EPCs) CD133+ have opened new perspectives for the treatment of ischemic areas after infarction. This preclinical study evaluated the effect of intramyocardial transplantation of purified or expanded human umbilical cord blood-derived CD133+ cells on the recovery of rats following acute myocardial infarction (AMI). Histology studies, electrocardiogram, and fluorescence in situ hybridization (FISH) were used to evaluate heart recovery...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29760599/vascular-erectile-dysfunction-and-subclinical-cardiovascular-disease
#10
Zain Gowani, S M Iftekhar Uddin, Mohammadhassan Mirbolouk, Dawar Ayyaz, Kevin L Billups, Martin Miner, David I Feldman, Michael J Blaha
Purpose of review: We review the recent literature on the hypothesized temporal relationship between subclinical cardiovascular disease (CVD), vascular erectile dysfunction (ED), and clinical CVD. In addition, we combine emerging research with expert consensus guidelines such as The Princeton Consensus III to provide a preventive cardiologist's perspective toward an ideal approach to evaluating and managing CVD and ED risk in patients. Recent findings: Development of ED was found to occur during the progression from subclinical CVD to clinical CVD...
December 2017: Current Sexual Health Reports
https://www.readbyqxmd.com/read/29759706/the-human-left-atrial-venous-circulation-as-a-vascular-route-for-atrial-pharmacological-therapies-effects-of-ethanol-infusion
#11
Miguel Valderrábano, Percy Francisco Morales, Moisés Rodríguez-Mañero, Candela Lloves, Paul A Schurmann, Amish S Dave
OBJECTIVES: This study catalogued the human venous left atrium (LA) circulation system and the ablative effects of ethanol in different branches. BACKGROUND: Vascular routes to target the LA could have significant therapeutic potential. Beyond the vein of Marshall (VOM), the fluoroscopic LA venous anatomy has not been described. METHODS: Patients undergoing ethanol infusion in the VOM as adjunctive therapy to atrial fibrillation (AF) catheter ablation were included in this study...
September 2017: JACC. Clinical Electrophysiology
https://www.readbyqxmd.com/read/29756391/rho-kinase-and-na-h-exchanger-mediate-endothelin-1-induced-pulmonary-arterial-smooth-muscle-cell-proliferation-and-migration
#12
John C Huetsch, Jasmine Walker, Clark Undem, Julie Lade, Xin Yun, Syeda Baksh, Haiyang Jiang, Ning Lai, Larissa A Shimoda
Excessive production of endothelin-1 (ET-1) has been observed in almost all forms of pulmonary hypertension. ET-1, a highly potent vasoconstrictor, can also potentiate pulmonary arterial smooth muscle cell (PASMC) growth and migration, both of which contribute to the vascular remodeling that occurs during the development of pulmonary hypertension. Increasing evidence indicates that alkalinization of intracellular pH (pHi ), typically due to activation of Na+ /H+ exchange (NHE), is associated with enhanced PASMC proliferation and migration...
May 2018: Physiological Reports
https://www.readbyqxmd.com/read/29755348/the-fibrin-cleavage-product-b%C3%AE-15-42-channels-endothelial-and-tubular-regeneration-in-the-post-acute-course-during-murine-renal-ischemia-reperfusion-injury
#13
Dania Fischer, Christopher Seifen, Patrick Baer, Michaela Jung, Christina Mertens, Bertram Scheller, Kai Zacharowski, Rainer Hofmann, Thorsten J Maier, Anja Urbschat
Early and adequate restoration of endothelial and tubular renal function is a substantial step during regeneration after ischemia reperfusion (IR) injury, occurring, e.g., in kidney transplantation, renal surgery, and sepsis. While tubular epithelial cell injury has long been of central importance, recent perception includes the renal vascular endothelium. In this regard, the fibrin cleavage product fibrinopeptide Bβ15-42 mitigate IR injury by stabilizing interendothelial junctions through its affinity to VE-cadherin...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29753912/biomimetic-soft-fibrous-hydrogels-for-contractile-and-pharmacologically-responsive-smooth-muscle
#14
Yonghui Ding, Xin Xu, Sadhana Sharma, Michael Floren, Kurt Stenmark, Stephanie J Bryant, Corey P Neu, Wei Tan
The ability to assess changes in smooth muscle contractility and pharmacological responsiveness in normal or pathological-relevant vascular tissue environments is critical to enable vascular drug discovery. However, major challenges remain in both capturing the complexity of in vivo vascular remodeling and evaluating cell contractility in complex, tissue-like environments. Herein, we developed a biomimetic fibrous hydrogel with tunable structure, stiffness, and composition to resemble the native vascular tissue environment...
May 10, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29749466/upregulated-14%C3%A2-3%C3%A2-3%C3%AE-aggravates-restenosis-by-promoting-cell-migration-following-vascular-injury-in-diabetic-rats-with-elevated-levels-of-free-fatty-acids
#15
Lishuai Feng, Chaoran Dou, Jianbo Wang, Chunyu Jiang, Xu Ma, Jingjing Liu
Mono‑unsaturated free fatty acids (FFAs) can serve as a predictive indicator of vascular restenosis following interventional therapy, particularly in individuals with high‑fat diet‑induced type 2 diabetes. However, the pathogenic mechanism remains to be fully elucidated. In the present study, the levels of tyrosine 3‑monooxygenase/tryptophan 5‑monooxygenase activation protein β (YWHAB; also known as 14‑3‑3β), in vascular smooth muscle cells (VSMCs) treated with different concentrations of oleic acid (OA) were examined by reverse transcription‑quantitative polymerase chain reaction and western blot analyses...
May 11, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29748368/cardiovascular-effects-of-new-oral-glucose-lowering-agents-dpp-4-and-sglt-2-inhibitors
#16
REVIEW
André J Scheen
Cardiovascular disease (CVD) is a major challenge in the management of type 2 diabetes mellitus. Glucose-lowering agents that reduce the risk of major cardiovascular events would be considered a major advance, as recently reported with liraglutide and semaglutide, 2 glucagon-like peptide-1 receptor agonists, and with empagliflozin and canagliflozin, 2 SGLT-2 (sodium-glucose cotransporter type 2) inhibitors, but not with DPP-4 (dipeptidyl peptidase-4) inhibitors. The present review is devoted to CV effects of new oral glucose-lowering agents...
May 11, 2018: Circulation Research
https://www.readbyqxmd.com/read/29747161/a-3d-human-renal-cell-carcinoma-on-a-chip-for-the-study-of-tumor-angiogenesis
#17
Chris P Miller, Connor Tsuchida, Ying Zheng, Jonathan Himmelfarb, Shreeram Akilesh
Tractable human tissue-engineered 3D models of cancer that enable fine control of tumor growth, metabolism, and reciprocal interactions between different cell types in the tumor microenvironment promise to accelerate cancer research and pharmacologic testing. Progress to date mostly reflects the use of immortalized cancer cell lines, and progression to primary patient-derived tumor cells is needed to realize the full potential of these platforms. For the first time, we report endothelial sprouting induced by primary patient tumor cells in a 3D microfluidic system...
May 7, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29745797/reversing-age-associated-arterial-dysfunction-insight-from-preclinical-models
#18
Venkateswara Reddy Gogulamudi, Jinjin Cai, Lisa A Lesniewski
Cardiovascular diseases (CVDs) remain the leading causes of death in the US, and advancing age is a primary risk factor. Impaired endothelium dependent dilation and increased stiffening of the arteries with aging are independent predictors of CVD. Increased tissue and systemic oxidative stress and inflammation underlie this age-associated arterial dysfunction. Calorie restriction (CR) is the most powerful intervention known to increase lifespan and improve age-related phenotypes, including arterial dysfunction...
May 10, 2018: Journal of Applied Physiology
https://www.readbyqxmd.com/read/29745737/the-safety-of-trifluridine-and-tipiracil-for-the-treatment-of-metastatic-colorectal-cancer
#19
Julia Martinez-Perez, M Carmen Riesco-Martinez, Rocio Garcia-Carbonero
TAS102 is an oral thymidine-based nucleoside analogue that has been approved for the treatment of patients with metastatic colorectal cancer (mCRC) previously treated with, or not candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-vascular endothelial growth factor (VEGF) agents and, if RAS wild-type, anti-epidermal growth factor receptor (EGFR) therapy. The pivotal RECOURSE phase III trial demonstrated a significant improvement in disease control rate, progression-free (PFS) and overall survival (OS) as compared with placebo in patients with refractory mCRC...
May 10, 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29745255/pannexin-1-channels-on-endothelial-cells-mediate-vascular-inflammation-during-lung-ischemia-reperfusion-injury
#20
Ashish K Sharma, Eric J Charles, Yunge Zhao, Adishesh K Narahari, Pranav K Baderdinni, Miranda E Good, Ulrike M Lorenz, Irving L Kron, Douglas A Bayliss, Kodi S Ravichandran, Brant E Isakson, Victor E Laubach
Ischemia-reperfusion injury (IRI), which involves inflammation, vascular permeability, and edema, remains a major challenge after lung transplantation. Pannexin 1 (Panx1) channels modulate cellular ATP release during inflammation. This study tests the hypothesis that endothelial Panx1 is a key mediator of vascular inflammation and edema after IR and that IRI can be blocked by Panx1 antagonism. A murine hilar ligation model of IRI was utilized whereby left lungs underwent 1 hour of ischemia and 2 hours of reperfusion...
May 10, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
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