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Vascular pharmacology

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https://www.readbyqxmd.com/read/28650002/cabozantinib-use-in-renal-cell-carcinoma
#1
A J Neuwelt, S Mathur, A T Johnson, E R Kessler, D W Bowles
In the last several years, many new drugs have been approved to treat metastatic renal cell carcinoma (RCC). Cabozantinib is a novel multikinase inhibitor with activity against vascular endothelial growth factor receptor (VEGFR), proto-oncogene tyrosine-protein kinase receptor Ret and other kinases that recently joined this impressive list of approved agents. Cabozantinib is an active agent in the preclinical and clinical setting, having recently demonstrated superiority over everolimus in a blinded, randomized phase III study of patients with progressive RCC after at least one prior line of antiangiogenic therapy...
May 2017: Drugs of Today
https://www.readbyqxmd.com/read/28649987/a-ppar%C3%AE-transcriptional-cascade-directs-adipose-progenitor-cell-niche-interaction-and-niche-expansion
#2
Yuwei Jiang, Daniel C Berry, Ayoung Jo, Wei Tang, Robert W Arpke, Michael Kyba, Jonathan M Graff
Adipose progenitor cells (APCs) reside in a vascular niche, located within the perivascular compartment of adipose tissue blood vessels. Yet, the signals and mechanisms that govern adipose vascular niche formation and APC niche interaction are unknown. Here we show that the assembly and maintenance of the adipose vascular niche is controlled by PPARγ acting within APCs. PPARγ triggers a molecular hierarchy that induces vascular sprouting, APC vessel niche affinity and APC vessel occupancy. Mechanistically, PPARγ transcriptionally activates PDGFRβ and VEGF...
June 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28648405/anti-inflammatory-activity-of-coptisine-free-base-in-mice-through-inhibition-of-nf-%C3%AE%C2%BAb-and-mapk-signaling-pathways
#3
Han-Bin Chen, Chao-Dan Luo, Jia-Li Liang, Zhen-Biao Zhang, Guo-Sheng Lin, Jia-Zhen Wu, Cai-Lan Li, Li-Hua Tan, Xiao-Bo Yang, Zi-Ren Su, Jian-Hui Xie, Hui-Fang Zeng
Coptisine is one of the main constituents of Coptis chinensis which has been widely used for the remedy of inflammatory disorders. Although the biological activities of coptisine have been well known, the pharmacological properties of its free base have seldomly been elucidated thus far. The aim of this study was to investigate the potential anti-inflammatory properties of coptisine free base (CFB, 8-hydroxy-7,8-dihydrocoptisine) on three animal models, namely xylene-induced ear edema, acetic acid-induced vascular permeability and carrageenan-induced paw edema...
June 22, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28645655/5-lipoxygenase-in-monocytes-emerges-as-a-therapeutic-target-for-intimal-hyperplasia-in-a-murine-wire-injured-femoral-artery
#4
Seung Eun Baek, Min A Jang, Seung Jin Lee, So Youn Park, Sun Sik Bae, Chi Dae Kim
Given the importance of leukotrienes in vascular inflammation induced by local tissue injury, this study investigated the role for 5-lipoxygenase (5-LO) in monocytes in the development of intimal hyperplasia. As a mechanistic study, the importance of monocyte 5-LO in monocyte-macrophage differentiation with subsequent infiltration in neointima was evaluated. In a mouse model of wire-injured femoral artery, intimal hyperplasia started as early as 2 wks after injury, and luminal area and blood flow were reduced due to increased neointima formation...
June 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28644070/particulate-matter-disrupts-human-lung-endothelial-cell-barrier-integrity-via-rho-dependent-pathways
#5
Ting Wang, Yuka Shimizu, Xiaomin Wu, Gabriel T Kelly, Xiaoyan Xu, Lichun Wang, Zhongqing Qian, Yin Chen, Joe G N Garcia
Increased exposure to ambient particulate matter (PM) is associated with elevated morbidity and mortality in patients with cardiopulmonary diseases and cancer. We and others have shown that PM induces lung microvascular barrier dysfunction which potentially enhances the systemic toxicity of PM. However, the mechanisms by which PM disrupts vascular endothelial integrity remain incompletely explored. We hypothesize that PM induces endothelial cell (EC) cytoskeleton rearrangement via Rho GTPase-dependent pathways to facilitate vascular hyperpermeability...
June 23, 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28643552/drug-induced-physeal-abnormalities-in-preclinical-toxicity-studies
#6
Kendall S Frazier
Most toxic physeal changes are characterized microscopically by altered chondrocyte development, proliferation, or maturation in the growth plate and eventually result in disordered appositional bone growth. Many therapeutic drugs directly or indirectly target proteins involved in chondrocytic differentiation and maturation pathways, so toxic physeal injury has become increasingly common in preclinical toxicologic pathology. While physeal dysplasia has been associated with several different drug classes including bisphosphonates, vascular endothelial growth factor receptor inhibitors, fibroblast growth factor receptor inhibitors, transforming growth factor beta receptor inhibitors, and vascular targeting agents, physeal changes often share similar morphologic features including thickening and disorganization of the hypertrophic layer, increased numbers of hypertrophic chondrocytes, altered mineralization of endochondral ossification, and/or increased thickness of subphyseal bone...
January 1, 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28641140/effect-of-c1-inh-on-ischemia-reperfusion-injury-in-a-porcine-limb-ex-vivo-perfusion-model
#7
Mai M Abdelhafez, Jane Shaw, Damian Sutter, Jonas Schnider, Yara Banz, Hansjörg Jenni, Esther Voegelin, Mihai A Constantinescu, Robert Rieben
Revascularization of an amputated limb within 4-6h is essential to avoid extensive ischemia/reperfusion (I/R) injury leading to vascular leakage, edema and tissue necrosis. I/R injury is a pathological inflammatory condition that occurs during reperfusion of an organ or tissue after prolonged ischemia. It is characterized by a complex crosstalk between endothelial cell activation and the activation of plasma cascades. Vasculoprotective pharmacological intervention to prevent I/R injury might be an option to prolong the time window between limb amputation and successful replantation...
June 19, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28638222/corticotropin-releasing-factor-stimulates-colonic-motility-via-muscarinic-receptors-in-the-rat
#8
Kyung-Jo Kim, Ki Bae Kim, Soon Man Yoon, Joung-Ho Han, Hee Bok Chae, Seon Mee Park, Sei Jin Youn
AIM: To measure exogenous corticotropin-releasing factor (CRF)-induced motility of the isolated rat colon and to demonstrate the effect of pharmacologic inhibition on CRF-induced motility. METHODS: The isolated vascularly-perfused rat colon was used. Luminal pressure was monitored via microtip catheter pressure transducers in the proximal and distal colon. At first, exogenous CRF was administered in a stepwise manner and the concentration of CRF yielding maximal colonic motility was selected...
June 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28637660/interleukin-33-induces-growth-regulated-oncogene-%C3%AE-expression-and-secretion-in-human-umbilical-vein-endothelial-cells
#9
Masayoshi Yamamoto, Katsuyuki Umebashi, Akinori Tokito, Junichi Imamura, Michihisa Jougasaki
Although interleukin (IL)-33, a member of the IL-1 cytokine family, plays pro-inflammatory roles in immune cells as an "alarmin", little is known regarding the biological actions of IL-33 on vascular endothelial cells. To investigate the effects of IL-33 on vascular endothelial cells, we first screened the IL-33-regulated proteins in human umbilical vein endothelial cells (HUVECs) using a dot blot array, and observed that IL-33 markedly increased growth-regulated oncogene (GRO)-α, a chemokine that is also known as CXCL1...
June 21, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28627793/increased-sympathetic-outflow-induces-adaptation-to-acute-experimental-pain
#10
Lior Dayan, Uri Hochberg, Hadas Nahman-Averbuch, Silviu Brill, Jacob N Ablin, Giris Jacob
BACKGROUND: There are interrelationships between the autonomic nervous system and pain. This study aims to explore the effect of different autonomic manipulations on pain perception and modulation. METHODS: Twenty healthy subjects (10 men and 10 women, mean age 25±3) participate in this single-blinded, semi-randomized, controlled study, which included 2 study visits. Warm and heat pain thresholds, conditioned pain modulation and pain adaptation were tested before and after administration of phenylephrine, clonidine, yohimbine and saline...
June 19, 2017: Pain Practice: the Official Journal of World Institute of Pain
https://www.readbyqxmd.com/read/28624099/cardiovascular-disease-and-cancer-evidence-for-shared-disease-pathways-and-pharmacologic-prevention
#11
REVIEW
Farzad Masoudkabir, Nizal Sarrafzadegan, Carolyn Gotay, Andrew Ignaszewski, Andrew D Krahn, Margot K Davis, Christopher Franco, Arya Mani
Cardiovascular disease (CVD) and cancer are leading causes of mortality and morbidity worldwide. Strategies to improve their treatment and prevention are global priorities and major focus of World Health Organization's joint prevention programs. Emerging evidence suggests that modifiable risk factors including diet, sedentary lifestyle, obesity and tobacco use are central to the pathogenesis of both diseases and are reflected in common genetic, cellular, and signaling mechanisms. Understanding this important biological overlap is critical and may help identify novel therapeutic and preventative strategies for both disorders...
June 2, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28623279/divergent-regulation-of-actin-dynamics-and-megakaryoblastic-leukemia-1-and-2-mkl1-2-by-camp-in-endothelial-and-smooth-muscle-cells
#12
Madeleine C Smith, Claire A Hudson, Tomomi E Kimura, Stephen J White, Graciela B Sala-Newby, Andrew C Newby, Mark Bond
Proliferation and migration of vascular smooth muscle cells (VSMCs) or endothelial cell (ECs) promote or inhibit, respectively, restenosis after angioplasty, vein graft intimal thickening and atherogenesis. Here we investigated the effects of cAMP-induced cytoskeletal remodelling on the serum response factor (SRF) co-factors Megakaryoblastic Leukemia-1 and -2 (MKL1 and MKL2) and their role in controlling VSMC and EC proliferation and migration. Elevation of cAMP using forskolin, dibutyryl-cAMP (db-cAMP), BAY60-6583 or Cicaprost induced rapid cytoskeleton remodelling and inhibited proliferation and migration in VSMCs but not EC...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28623080/increased-constitutive-nitric-oxide-production-by-whole-body-periodic-acceleration-ameliorates-alterations-in-cardiomyocytes-associated-with-utrophin-dystrophin-deficiency
#13
Jose R Lopez, Juan Kolster, Rui Zhang, Jose Adams
Duchenne Muscular Dystrophy (DMD) cardiomyopathy is a progressive lethal disease caused by the lack of the dystrophin protein in the heart. The most widely used animal model of DMD is the dystrophin-deficient mdx mouse; however, these mice exhibit a mild dystrophic phenotype with heart failure only late in life. In contrast, mice deficient for both dystrophin and utrophin (mdx/utrn(-/-), or dKO) can be used to model severe DMD cardiomyopathy where pathophysiological indicators of heart failure are detectable by 8-10weeks of age...
June 13, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28620995/effects-of-tilianin-on-proliferation-migration-and-tgf-%C3%AE-smad-signaling-in-rat-vascular-smooth-muscle-cells-induced-with-angiotensin-ii
#14
Wenjiang Cao, Na Hu, Yong Yuan, Jiang Cheng, Xinhong Guo, Yanfang Wang, Xinchun Wang, Ping Hu
Flavonoid Tilianin was isolated from Dracocephalum moldavica, and its pharmacological mechanism on proliferation, migration and the TGF-β/Smad signaling pathway in rat vascular smooth muscle cells (VSMCs) induced with Angiotensin II (Ang II) was systematically evaluated. Primary rat VSMCs were stimulated with Ang II to induce proliferation. The cells were then treated with Tilianin for 24 or 48 h. MTT assay and Transwell assays were used to evaluate the effects of Tilianin on proliferation and migration. The expression of intracellular proliferating cell nuclear antigen (PCNA), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were measured by immunohistochemistry as verification of effects on proliferation and migration...
June 16, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28618986/inflammatory-and-oxidative-stress-markers-as-indicator-of-atherogenesis-in-rats-antioxidants-as-preventive-pharmacological-methods
#15
Maria Del Carmen Baez, Mariana Tarán, María de La Paz Scribano, Ariel Balceda, Carla Buonanotte, Sergio Blencio, Ismael Fonseca, Monica Moya
The oxidative process in atherogenesis generated by proinflammatory induction and response to antioxidants vitamins in an experimental model were analyzed. METHODS: Male rats were used: (A)Control, (B)Control+vitamin E plus C, (C)Hyperfibrinogenemia and (D)Hyperfibrinogenemia+vitamins E plus C. Hyperfibrinogenemia induced by daily injection of adrenaline (0.1mg/day/rat) for 120 days. TREATMENT: 3.42 mg/kg of vitamin E plus 2.14 mg/kg of vitamin C, fifteen days after induction...
June 16, 2017: Anti-inflammatory & Anti-allergy Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28617071/an-endothelial-link-between-the-benefits-of-physical-exercise-in-dementia
#16
Lianne J Trigiani, Edith Hamel
The current absence of a disease-modifying treatment for Alzheimer's disease (AD) and vascular cognitive impairment and dementia (VCID) highlights the necessity for investigating the benefits of non-pharmacological approaches such as physical exercise (PE). Although evidence exists to support an association between regular PE and higher scores on cognitive function tests, and a slower rate of cognitive decline, there is no clear consensus on the underlying molecular mechanisms of the advantages of PE. This review seeks to summarize the positive effects of PE in human and animal studies while highlighting the vascular link between these benefits...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28615322/in-vivo-manipulation-of-the-extracellular-matrix-induces-vascular-regression-in-a-basal-chordate
#17
Delany Rodriguez, Brian P Braden, Scott W Boyer, Daryl A Taketa, Leah Setar, Chris Calhoun, Alessandro Di Maio, Adam Langenbacher, Megan T Valentine, Anthony W De Tomaso
We investigated the physical role of the extracellular matrix in vascular homeostasis in the basal chordate Botryllus schlosseri, which has a large, transparent extracorporeal vascular network encompassing areas >100 cm(2) We found that the collagen crosslinking enzyme lysyl oxidase is expressed in all vascular cells, and that in vivo inhibition using ß-aminopropionitrile (BAPN) caused a rapid, global regression of the entire network, with some vessels regressing >10 mm within 16 hours. BAPN treatment changed the ultrastructure of collagen fibers in the vessel basement membrane, and the kinetics of regression were dose-dependent...
June 14, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28615146/novel-insights-into-acute-kidney-injury-chronic-kidney-disease-continuum-and-the-role-of-renin-angiotensin-system
#18
REVIEW
Yu-Hsiang Chou, Tao-Min Huang, Tzong-Shinn Chu
Acute kidney injury (AKI) is an independent risk factor for chronic kidney disease (CKD). If injury is mild, a repair process can be adaptive and lead to complete renal recovery. However, severe injury will be accompanied by a maladaptive repair which usually leads to nephron loss, fibrosis, vascular rarefaction, and chronic inflammation. Although various mechanisms underlying AKI-CKD transition have been explored, no intervention has been proved effective to block the transition until very recently. A lack of consensus for monitoring renal function and defining renal recovery after AKI should be the reasons for the slow advance in the discovery of a timely pharmacologic treatment to block AKI-CKD transition...
June 11, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28612103/dihydromyricetin-protects-human-umbilical-vein-endothelial-cells-from-injury-through-erk-and-akt-mediated-nrf2-ho-1-signaling-pathway
#19
Yun Luo, Shan Lu, Xi Dong, Lijia Xu, Guibo Sun, Xiaobo Sun
Atherosclerosis-related cardiovascular disease is the predominant cause of death worldwide. Ox-LDL-induced vascular endothelial cell injury is a major factor in the pathogenesis of atherosclerosis. Dihydromyricetin (DMY) is a flavonoid extracted from vine tea that exerts multiple pharmacological activities, including cardio-protective, anti-tumor, and anti-oxidative effects. However, it is unreported that DMY shows protective effects on ox-LDL-induced endothelial cell injury. In this study, we used an ox-LDL injured human umbilical vein endothelial cell (HUVEC) in vitro model to explore the protective effects and mechanism of DMY...
June 13, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28608258/extracts-of-chrysanthemum-zawadskii-attenuate-oxidative-damage-to-vascular-endothelial-cells-caused-by-a-highly-reducing-sugar
#20
Hyun-Sook Kim
Endothelial cells are considered candidates for involvement in the pathogenesis of diabetic vascular complications, and prevention of endothelial cell damage may be important in pharmacological attempts to prevent such complications. In the present study, I explored whether extracts of Chrysanthemum zawadskii (CZE) could prevent oxidative damage and dysfunction of a vascular endothelial cell line caused by the highly reducing sugar, 2-deoxy-D-ribose (dRib), and dysfunction of a vascular endothelial cell line...
June 12, 2017: Cytotechnology
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