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Vascular pharmacology

Adel Schwertani, Hong Y Choi, Jacques Genest
PURPOSE OF REVIEW: Plasma levels of HDL cholesterol are a biomarker of cardiovascular health but not a therapeutic target, as demonstrated by the failure of pharmacological modulation of HDL cholesterol to prevent or treat atherosclerotic cardiovascular disease. In health, HDL particles exert pleiotropic effects against atherosclerosis, including cholesterol removal from foam cells, vasodilatory effects through vascular endothelial cell nitric oxide production, decreased vascular inflammation and oxidative damage, endothelial cell proliferation and antiapoptotic effects...
March 19, 2018: Current Opinion in Cardiology
Jolien Fleur Leijenaar, Geert Jan Groeneveld, Wiesje Maria van der Flier, Philip Scheltens, Erica Surya Klaassen, Henry Chanoch Weinstein, Geert Jan Biessels, Frederik Barkhof, Niels Daniël Prins
BACKGROUND: People with vascular cognitive impairment (VCI) constitute a clinically heterogeneous group, but previous symptomatic drug trials in VCI did not take this clinical heterogeneity into account. Executive dysfunction and memory impairment are the cognitive domains that are most frequently impaired in VCI, and these impairments are likely to reflect vascular damage to specific neurotransmitter systems, which opens the possibility for targeted symptomatic treatment directed at specific neurotransmitters...
March 20, 2018: JMIR Research Protocols
Kay D Beharry, Charles L Cai, Taimur Ahmad, Sibel Guzel, Gloria B Valencia, Jacob V Aranda
Neonatal intermittent hypoxia (IH) followed by re-oxygenation in normoxia or supplemental oxygen (IHR) increases the risk for severe retinopathy of prematurity (ROP). The exact timing for the onset of retinal damage which may guide strategic interventions during retinal development, is unknown. We tested the hypothesis that chronic exposure of the immature retina to neonatal IH induces early manifestations of retinal damage that can be utilized as key time points for strategic pharmacologic intervention. Newborn rats were exposed to IH within 2 hours of birth (P0) until P14, or allowed to recover in room air (RA) from P14 to P21 (IHR)...
2018: Journal of Nature and Science
Anton G Kutikhin, Maxim Yu Sinitsky, Arseniy E Yuzhalin, Elena A Velikanova
The blood flow through vessels produces a tangential, or shear, stress sensed by their innermost layer (i.e., endothelium) and representing a major hemodynamic force. In humans, endothelial repair and blood vessel formation are mainly performed by circulating endothelial progenitor cells (EPCs) characterized by a considerable expression of vascular endothelial growth factor receptor 2 (VEGFR2), CD34, and CD133, pronounced tube formation activity in vitro, and strong reendothelialization or neovascularization capacity in vivo...
March 13, 2018: Journal of Molecular and Cellular Cardiology
Nicholas Beazley-Long, Catherine Elizabeth Moss, William Robert Ashby, Samuel Marcus Bestall, Fatimah Almahasneh, Alexandra Margaret Durrant, Andrew Vaughan Benest, Zoe Blackley, Kurt Ballmer-Hofer, Masanori Hirashima, Richard Phillip Hulse, David Owen Bates, Lucy Frances Donaldson
Chronic pain can develop in response to conditions such as inflammatory arthritis. The central mechanisms underlying the development and maintenance of chronic pain in humans are not well elucidated although there is evidence for a role of microglia and astrocytes. However in pre-clinical models of pain, including models of inflammatory arthritis, there is a wealth of evidence indicating roles for pathological glial reactivity within the CNS. In the spinal dorsal horn of rats with painful inflammatory arthritis we found both a significant increase in CD11b+ microglia-like cells and GFAP+ astrocytes associated with blood vessels, and the number of activated blood vessels expressing the adhesion molecule ICAM-1, indicating potential glio-vascular activation...
March 13, 2018: Brain, Behavior, and Immunity
Regina Trollmann, Theresa Mühlberger, Mandy Richter, Gudrun Boie, Andreas Feigenspan, Florian Brackmann, Susan Jung
Angiogenesis due to hypoxic-ischemic (HI) injury represents a crucial compensatory mechanism of the developing brain that is mainly regulated by hypoxia-inducible transcription factors (HIF). Pharmacological stimulation of HIF is suggested as a neuroprotective option, however, studies of its effects on vascular development are limited. We analyzed the influence of the prolyl-4-hydroxylase inhibitor (PHI), FG-4497, and erythropoietin (rhEPO) on post-hypoxic angiogenesis (angiogenic growth factors, vessel structures) in the developing mouse brain (P7) assessed after a regeneration period of 72 h...
March 13, 2018: Brain Research
Christina H Stuelten, Carole A Parent, Denise J Montell
Metastasis remains the greatest challenge in the clinical management of cancer. Cell motility is a fundamental and ancient cellular behaviour that contributes to metastasis and is conserved in simple organisms. In this Review, we evaluate insights relevant to human cancer that are derived from the study of cell motility in non-mammalian model organisms. Dictyostelium discoideum, Caenorhabditis elegans, Drosophila melanogaster and Danio rerio permit direct observation of cells moving in complex native environments and lend themselves to large-scale genetic and pharmacological screening...
March 16, 2018: Nature Reviews. Cancer
Yuh-Charn Lin, Chun-Yu Liu, Reiji Kannagi, Ruey-Bing Yang
OBJECTIVE: SCUBE2 (signal peptide-CUB-EGF domain-containing protein 2), expressed on the endothelial cell surface, functions as a novel coreceptor for VEGFR2 (vascular endothelial growth factor receptor 2) and enhances VEGF-induced signaling in adult angiogenesis. However, whether SCUBE2 plays a role in pathological angiogenesis and whether anti-SCUBE2 antibody is an effective strategy for blocking tumor angiogenesis remain unknown. The aim of this study was to investigate the pathological role and targeting therapy of SCUBE2 in tumor vasculature...
March 15, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Asuka Kikuchi, Fairuz Binti Mohammadi Nasir, Akie Inami, Attayeb Mohsen, Shoichi Watanuki, Masayasu Miyake, Kazuko Takeda, Daigo Koike, Takayasu Ito, Junpei Sasakawa, Rin Matsuda, Kotaro Hiraoka, Marcus Maurer, Kazuhiko Yanai, Hiroshi Watabe, Manabu Tashiro
OBJECTIVE: Antihistamines often have sedative side effects. This was the first study to measure regional cerebral glucose (energy) consumption and hemodynamic responses in young adults during cognitive tests after antihistamine administration. METHODS: In this double-blind, placebo-controlled, three-way crossover study, 18 healthy young Japanese men received single doses of levocetirizine 5 mg and diphenhydramine 50 mg at intervals of at least six days. Subjective feeling, task performances, and brain activity were evaluated during three cognitive tests (word fluency, two-back, and Stroop)...
March 13, 2018: Human Psychopharmacology
M Rroji, G Spasovski
Secondary hyperparathyroidism (SHPT) is common among patients with end-stage renal disease (ESRD). SHPT is associated with high-turnover bone disease, interstitial and vascular calcifications, cardiovascular morbidity and mortality. The pharmacological management of SHPT has progressed in recent years. The introduction of targeted therapies, such as selective vitamin D receptors activators and calcium-sensing receptor modulators, offers an increased opportunity to adequately control elevated parathyroid hormone (PTH), especially in patients with chronic kidney disease under dialysis treatment...
March 12, 2018: International Urology and Nephrology
Georgia Brown, Tilman Humpl
PURPOSE OF REVIEW: Pulmonary vascular disease (PVD) complicates the course of many cardiovascular, pulmonary and other systemic diseases in children. The physiological sequelae (pulmonary hypertension and elevated pulmonary vascular resistance) can overwhelm the right ventricle and lead to circulatory collapse. Despite the common end-point, the preceding pathophysiology is complex and variable and requires a tailored approach to diagnosis and management. In this article, we will review the most recent evidence and explore an approach to current controversies in the diagnosis and management of common or challenging patient subgroups...
March 9, 2018: Current Opinion in Pediatrics
Rui Guo, Xiaoxiao Zhang, Jin Su, Haiyu Xu, Yanqiong Zhang, Fangbo Zhang, Defeng Li, Yi Zhang, Xuefeng Xiao, Shuangcheng Ma, Hongjun Yang
BACKGROUND: Quality marker (Q-markers) has been proposed as a novel concept for quality evaluation and standard elaboration of traditional Chinese medicine (TCM). Xin-Su-Ning capsule (XSNC) has been extensively used for the treatment of arrhythmia with the satisfactory therapeutic effects in clinics. However, it is lack of reliable and effective Q-markers of this prescription. PURPOSE: To identify potential Q-markers of XSNC against arrhythmia. STUDY DESIGN: An integrative pharmacology-based investigation was performed...
February 10, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Umberto Capasso Palmiero, Lavinia Morosi, Ezia Bello, Marianna Ponzo, Roberta Frapolli, Cristina Matteo, Mariella Ferrari, Massimo Zucchetti, Lucia Minoli, Marcella De Maglie, Pierpaolo Romanelli, Massimo Morbidelli, Maurizio D'Incalci, Davide Moscatelli
The improvement of the pharmacological profile of lipophilic drug formulations is one of the main successes achieved using nanoparticles (NPs) in medicine. However, the complex synthesis procedure and numerous post-processing steps hamper the cost-effective use of these formulations. In this work, an approach which requires only a syringe to produce self-assembling biodegradable and biocompatible poly(caprolactone)-based NPs is developed. The effective synthesis of monodisperse NPs has been made possible by the optimization of the block copolymer synthesized via a combination of ring opening polymerization and reversible addition-fragmentation chain transfer polymerization...
March 7, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Narahari Rishitha, Arunachalam Muthuraman
BACKGROUND: Quercetin is a major flavonoid in various plants. It possesses the multiple pharmacological actions like vascular integrity and regulatory action of the blood-brain barrier. AIMS: The present study is focused on evaluating the role of solid lipid nanoparticle of quercetin in pentylenetetrazole (PTZ) induced cognitive impairment of Danio rerio species. MAIN METHODS: The memory impairment of zebrafish was induced by exposing of PTZ in 7...
March 6, 2018: Life Sciences
Xiang-Yong Liu, Hai-Xiao Xu, Jian-Kui Li, Dong Zhang, Xiao-Hong Ma, Li-Na Huang, Jun-Hong Lü, Xiao-Zhi Wang
Damage to the endothelial glycocalyx is a critical factor in increased pulmonary vascular permeability, which is the basic pathological feature of acute respiratory distress syndrome (ARDS). Neferine (Nef), a bisbenzylisoquinoline alkaloid isolated from green seed embryos of Nelumbo nucifera Gaertn , has extensive pharmacological activity. In this study, we showed that Nef reduced lung-capillary permeability, down-regulated the production of cytokines (IL-1β, IL-6, TNF-α, and IL-10) and inhibited the activation of the NF-κB signaling pathway in mice with lipopolysaccharide (LPS)-induced ARDS...
2018: Frontiers in Physiology
Mehdi Rajabi, Murat Yalcin, Shaker A Mousa
In the angiogenesis process, integrins, which are members of a family of cell surface transmembrane receptors, play a critical role particularly in blood vessel formation and the local release of vascular growth factors. Thyroid hormones such as l-thyroxine (T4 ) and 3,5,3'-triiodo-l-thyronine (T3 ) promote angiogenesis and tumor cell proliferation via integrin αvβ3 receptor. At or near an arginine-glycine-aspartate (RGD) recognition site on the binding pocket of integrin αv β3 , tetraiodothyroacetic acid (tetrac, a deaminated derivative of T4 ) is a thyrointegrin receptor antagonist and blocks the actions of T3 and T4 as well as different growth factors-mediated angiogenesis...
February 26, 2018: Bioorganic & Medicinal Chemistry Letters
Weichen Huang, Mingcheng Huang, Hui Ouyang, Jingwen Peng, Jiang Liang
Oridonin, an active diterpenoid compound isolated from the plant Rabdosia Rrubescens, has various pharmacological activities, including antioxidant, anti-tumor capacities and anti-inflammation. In the present study, we explore the role of oridonin in regulating endothelial inflammation and its underlying mechanism. Endothelial cell-monocyte interaction was detected by Leukocyte-endothelium Adhesion Assay. The protein expression was measured by Western blot. NF-κB p65 translocation was measured by immunofluorescence...
March 5, 2018: European Journal of Pharmacology
Tatyana Merkulova-Rainon, Chris S Mantsounga, Dong Broquères-You, Cristina Pinto, José Vilar, Diana Cifuentes, Philippe Bonnin, Nathalie Kubis, Daniel Henrion, Jean-Sébastien Silvestre, Bernard I Lévy
The pathophysiology of sporadic Alzheimer's disease (AD) remains uncertain. Along with brain amyloid-β (Aβ) deposits and neurofibrillary tangles, cerebrovascular dysfunction is increasingly recognized as fundamental to the pathogenesis of AD. Using an experimental model of limb ischemia in transgenic APPPS1 mice, a model of AD (AD mice), we showed that microvascular impairment also extends to the peripheral vasculature in AD. At D70 following femoral ligation, we evidenced a significant decrease in cutaneous blood flow (- 29%, P < 0...
March 7, 2018: Angiogenesis
Almesh Kadakol, Vajir Malek, Santosh Kumar Goru, Anuradha Pandey, Anil Bhanudas Gaikwad
OBJECTIVES: Although cardioprotective effects of telmisartan are well explored, its effects on epigenetic alterations associated with type 2 diabetic (T2D) cardiomyopathy remain unmapped. Thus, the present study was designed to evaluate the potential of esculetin and telmisartan combination to reverse histone posttranslational modifications (PTMs) in curbing T2D cardiomyopathy. MATERIALS AND METHODS: T2D was induced by high-fat diet feeding along with low dose of streptozotocin (35 mg/kg, I...
September 2017: Indian Journal of Pharmacology
Karolina Losenkova, Mariachiara Zuccarini, Mikko Helenius, Guillaume Jacquemet, Evgenia Gerasimovskaya, Camilla Tallgren, Sirpa Jalkanen, Gennady G Yegutkin
Intravascular ATP and adenosine have emerged as important regulators of endothelial barrier function, vascular remodeling and neovascularization at various pathological states, including hypoxia, inflammation and oxidative stress. By using human umbilical vein endothelial cells (HUVEC) and bovine vasa vasorum endothelial cells (VVEC) as representatives of macro- and microvessel phenotypes, this study was undertaken to evaluate cellular mechanisms contributing to physiological adaptation of vascular endothelium to hypoxia, with a particular emphasis on ectoenzymatic purine-converting activities and their link to intracellular ATP homeostasis and signaling pathways...
March 4, 2018: Biochimica et Biophysica Acta
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