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Womens Studies International Forum
Available online 20 February 2018
Activation of endothelial TrkB receptors induces relaxation of resistance arteries
Publication date: Available online 20 February 2018
Source:Vascular Pharmacology Author(s): P. Totoson, M. Pedard, C. Marie, C. Demougeot While brain-derived neurotrophic factor (BDNF) was previously reported to induce relaxation of conduit artery, whether the BDNF/TrkB (tropomyosin-related kinase) pathway is involved in the tone control of resistance arteries is not known. This study investigated TrkB receptors levels/localization and the vasomotor effect of the TrkB receptor agonist LM22A-4 in isolated third-order mesenteric arteries from rats. Immunostaining revealed the presence of both full-length and truncated TrkB receptors, especially at the endothelial level. By using wire myography, LM22A-4 induced vascular relaxation that was significantly decreased by cyclotraxin B as a non-competitive TrkB antagonist and fully prevented by endothelium removal. Inhibitors of NO, EDHF, PGI2 production and the PI3K/Akt pathways separately reduced LM22A-4 induced-relaxation. By contrast, inhibition of Raf/MEK, PLC
Available online 15 February 2018
The morphological and molecular mechanisms of epithelial/endothelial-to-mesenchymal transition and its involvement in atherosclerosis
Publication date: Available online 20 February 2018
Source:Vascular Pharmacology Author(s): M. Wesseling, T.R. Sakkers, S.C.A. de Jager, G. Pasterkamp, M.J. Goumans Cell transdifferentiation occurs during cardiovascular development or remodeling either as a pathologic feature in the progression of disease or as a response to injury. Endothelial-to-Mesenchymal Transition (EndMT) is a process that is classified as a specialized form of Epithelial-to-Mesenchymal Transition (EMT), in which epithelial cells lose their epithelial characteristics and gain a mesenchymal phenotype. During transdifferentiation, cells lose both cell-cell contacts and their attachment to the basement membrane. Subsequently, the shape of the cells changes from a cuboidal to an elongated shape. A rearrangement of actin filaments facilitates the cells to become motile and prime their migration into the underlying tissue. EMT is a key process during embryonic development, wound healing and tissue regeneration, but has also been implicated in pathophysiological processes, such organ fibrosis and tumor metastases. EndMT has been associated with additional pathophysiological processes in cardiovascular related diseases, including atherosclerosis. Recent studies prove a significant role for EndMT in the progression and destabilization of atherosclerotic plaques, as a consequence of EndMT-derived fibroblast infiltration and the increased secretion of matrix metalloproteinase respectively. In this review we will discuss the essential molecular and morphological mechanisms of EMT and EndMT, along with their common denominators and key differences. Finally, we will discuss the role of EMT/EndMT in developmental and pathophysiological processes, focusing on the potential role of EndMT in atherosclerosis in more depth.

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Available online 13 February 2018
Renal perivascular adipose tissue: Form and function
Publication date: Available online 15 February 2018
Source:Vascular Pharmacology Author(s): Carolina Baraldi A. Restini, Alex Ismail, Ramya K. Kumar, Robert Burnett, Hannah Garver, Gregory D. Fink, Stephanie W. Watts Renal sympathetic activity affects blood pressure in part by increasing renovascular resistance via release of norepinephrine (NE) from sympathetic nerves onto renal arteries. Here we test the idea that adipose tissue adjacent to renal blood vessels, i.e. renal perivascular adipose tissue (RPVAT), contains a pool of NE which can be released to alter renal vascular function. RPVAT was obtained from around the main renal artery/vein of the male Sprague Dawley rats. Thoracic aortic PVAT and mesenteric PVAT also were studied as brown-like and white fat comparators respectively. RPVAT was identified as a mix of white and brown adipocytes, because of expression of both brown-like (e.g. uncoupling protein 1) and white adipogenic genes. All PVATs contained NE (ng/g tissue, RPVAT:524
Available online 9 February 2018
Human adipose tissue-derived stromal cells in combination with exogenous stimuli facilitate three-dimensional network formation of human endothelial cells derived from various sources
Publication date: Available online 13 February 2018
Source:Vascular Pharmacology Author(s): Dominique Manikowski, Birgit Andr
Available online 9 February 2018
Bleeding predictors in patients following venous thromboembolism treated with vitamin K antagonists: Association with increased number of single nucleotide polymorphisms
Publication date: Available online 9 February 2018
Source:Vascular Pharmacology Author(s): Agata Hanna Bryk, Ewa Wypasek, Krzysztof Plens, Magdalena Awsiuk, Anetta Undas Introduction Single nucleotide polymorphisms (SNP) in genes encoding proteins involved in metabolism and action of vitamin K antagonists (VKA) affect anticoagulation stability. We investigated how those polymorphisms influence bleeding rates in patients following venous thromboembolism (VTE). Materials and methods In 324 patients following unprovoked VTE, 143 (44%) on warfarin and 181 (56%) on acenocoumarol, we recorded bleedings within the preceding 24
Available online 6 February 2018
Acarbose inhibits the proliferation and migration of vascular smooth muscle cells via targeting Ras signaling
Publication date: Available online 9 February 2018
Source:Vascular Pharmacology Author(s): Meng-Hsun Yu, Ming-Cheng Lin, Chien-Ning Huang, Kuei-Chuan Chan, Chau-Jong Wang Atherosclerosis involves the proliferation and migration of vascular smooth muscle cells (VSMCs). The migration of VSMCs from the media into the intima and their subsequent proliferation are important processes in neointima formation in atherosclerosis and restenosis after percutaneous coronary interventions. Acarbose, an alpha-glucosidase inhibitor, has been demonstrated to not affect serum levels of glucose and decrease the progression of intima-media thickening in rabbits fed with a high cholesterol diet (HCD). We previously showed that increased Ras protein levels enhanced the migration of TNF-
Available online 6 February 2018
Diabetic macroangiopathy: Pathogenetic insights and novel therapeutic approaches with focus on high glucose-mediated vascular damage
Publication date: Available online 6 February 2018
Source:Vascular Pharmacology Author(s): Rosalinda Madonna, Damiana Pieragostino, Carmela Rita Balistreri, Claudia Rossi, Yong-Jian Geng, Piero Del Boccio, Raffaele De Caterina Diabetic macroangiopathy a specific form of accelerated atherosclerosis is characterized by intra-plaque new vessel formation due to excessive/abnormal neovasculogenesis and angiogenesis, increased vascular permeability of the capillary vessels, and tissue edema, resulting in frequent atherosclerotic plaque hemorrhage and plaque rupture. Mechanisms that may explain the premature and rapidly progressive nature of atherosclerosis in diabetes are multiple, and to a large extent still unclear. However, mechanisms related to hyperglycemia certainly play an important role. These include a dysregulated vascular regeneration. In addition, oxidative and hyperosmolar stresses, as well as the activation of inflammatory pathways triggered by a dysregulated activation of membrane channel proteins aquaporins, have been recognized as key events. Here, we review recent knowledge of cellular and molecular pathways of macrovascular disease related to hyperglycemia in diabetes. We also here highlight how new insights into pathogenic mechanisms of vascular damage in diabetes may indicate new targets for prevention and treatment.

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Available online 6 February 2018
LncRNAs in vascular biology and disease
Publication date: Available online 6 February 2018
Source:Vascular Pharmacology Author(s): Viorel Simion, Stefan Haemmig, Mark W. Feinberg Accumulating studies indicate that long non-coding RNAs (lncRNAs) play important roles in the regulation of diverse biological processes involved in homeostatic control of the vessel wall in health and disease. However, our knowledge of the mechanisms by which lncRNAs control gene expression and cell signaling pathways is still nascent. Furthermore, only a handful of lncRNAs has been functionally evaluated in response to pathophysiological stimuli or in vascular disease states. For example, lncRNAs may regulate endothelial dysfunction by modulating endothelial cell proliferation (e.g. MALAT1, H19) or angiogenesis (e.g. MEG3, MANTIS). LncRNAs have also been implicated in modulating vascular smooth muscle cell (VSMC) phenotypes or vascular remodeling (e.g. ANRIL, SMILR, SENCR, MYOSLID). Finally, emerging studies have implicated lncRNAs in leukocytes activation (e.g. lincRNA-Cox2, linc00305, THRIL), macrophage polarization (e.g. GAS5), and cholesterol metabolism (e.g. LeXis). This review summarizes recent findings on the expression, mechanism, and function of lncRNAs implicated in a range of vascular disease states from mice to human subjects. An improved understanding of lncRNAs in vascular disease may provide new pathophysiological insights and opportunities for the generation of a new class of RNA-based biomarkers and therapeutic targets.

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Available online 3 February 2018
The mechanisms behind decreased internalization of angiotensin II type 1 receptor
Publication date: Available online 6 February 2018
Source:Vascular Pharmacology Author(s): Jingwei Bian, Suli Zhang, Ming Yi, Mingming Yue, Huirong Liu The internalization of angiotensin II type 1 receptor (AT1R) plays an important role in maintaining cardiovascular homeostasis. Decreased receptor internalization is closely related to cardiovascular diseases induced by the abnormal activation of AT1R, such as hypertension. However, the mechanism behind reduced AT1R internalization is not fully understood. This review focuses on four parts of the receptor internalization process (the combination of agonists and receptors, receptor phosphorylation, endocytosis, and recycling) and summarizes the possible mechanisms by which AT1R internalization is reduced based on these four parts of the process. (1) The agonist has a large molecular weight or a stronger ability to hydrolyze phosphatidylinositol 4,5-bisphosphate (PtdIns (4,5) P2), which can increase the consumption of PtdIns (4,5) P2. (2) AT1R phosphorylation is weakened because of an abnormal function of phosphorylated kinase or changes in phospho-barcoding and GPCR
Available online 2 February 2018
Linking diabetic vascular complications with LncRNAs
Publication date: Available online 3 February 2018
Source:Vascular Pharmacology Author(s): Amy Leung, Vishnu Amaram, Rama Natarajan Diabetes leads to markedly accelerated rates of many associated macrovascular complications like hypertension and atherosclerosis, and microvascular complications like nephropathy and retinopathy. High glucose, the hallmark of diabetes, drives changes in vascular and inflammatory cells that promote the development of these complications. Understanding the molecular processes involved in the development of diabetes and its debilitating complications can lead to much needed newer clinical therapies. Recently, long-noncoding RNAs (lncRNAs) have been shown to be important in the biology of vascular cells and there is growing evidence that lncRNAs are also involved in the cell biology relevant to diabetic vascular complications. In this review, we provide an overview of lncRNAs that function in vascular cells, and those that have been linked to diabetic complications.

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February 2018
Inhibition of miR-29b suppresses MAPK signaling pathway through targeting SPRY1 in atherosclerosis
Publication date: Available online 2 February 2018
Source:Vascular Pharmacology Author(s): Zhen Lu, Feng Wang, Pei Yu, Xue Wang, Yuan Wang, Song-tao Tang, Hua-qing Zhu The treatment of atherosclerosis (AS), a severe condition associated with the pathogenesis of cardiovascular diseases (CVDs), is still not satisfactory worldwide. In this study, we aim to investigate whether protein sprout homologue 1 (SPRY1), a upstream mediator of MAPK signal pathway, is the target of miR-29b in vascular endothelium during the development of AS. ApoE
February 2018
Editorial Board
Publication date: February 2018
Source:Vascular Pharmacology, Volume 101

February 2018
Nanotechnology and primary hemostasis: Differential effects of nanoparticles on platelet responses
Publication date: February 2018
Source:Vascular Pharmacology, Volume 101 Author(s): Mar
February 2018
Effects of endurance training on serum lipids
Publication date: February 2018
Source:Vascular Pharmacology, Volume 101 Author(s): Kati Fikenzer, Sven Fikenzer, Ulrich Laufs, Christian Werner Background and aims Physical activity is recommended as part of the lifestyle modification for the treatment of hyperlipidemia, however, the literature reports heterogeneous quantitative effects of exercise on serum lipids. We therefore reviewed the effects of aerobic exercise on serum lipids with special focus on the training effectiveness. Methods Data regarding effects of endurance training (ET) on total Cholesterol (TC), LDL-Cholesterol (LDL-C), HDL-Cholesterol (HDL-C) and triglycerides (TG) were evaluated in a selective literature search. To account for the observed heterogeneity of the training interventions, studies were analyzed according to effectiveness (duration, intensity, frequency) of training. Results Unselected training intervention studies did not exert significant effects on serum LDL-C but showed minor positive effects on HDL-C and TG. Effective endurance training - defined as endurance training performed by an intensity of 6575% of the heart rate reserve (corresponding to 7585% maximum heart rate or 6580% VO2max) for a duration of 4050min per training unit on 34days/week over a period of 2640weeks showed improvement of serum lipids. Effective training lowered TC by
February 2018
Lactadherin: An unappreciated haemostasis regulator and potential therapeutic agent
Publication date: February 2018
Source:Vascular Pharmacology, Volume 101 Author(s): Agnieszka Kami
February 2018
Chlorogenic acid attenuates diabetic retinopathy by reducing VEGF expression and inhibiting VEGF-mediated retinal neoangiogenesis
Publication date: February 2018
Source:Vascular Pharmacology, Volume 101 Author(s): Xiyu Mei, Lingyu Zhou, Tianyu Zhang, Bin Lu, Yuchen Sheng, Lili Ji Diabetic retinopathy (DR) is one of the most common and serious complications of diabetes mellitus (DM). This study aims to investigate the amelioration of chlorogenic acid (CGA) on proliferative DR (PDR) via focusing on inhibiting retinal neoangiogenesis. CGA reduced the increased cell proliferation, migration and tube formation induced by vascular endothelial growth factor (VEGF) in human retinal endothelial cells (HREC) and choroid-retinal endothelial RF/6A cells. CGA abrogated VEGF-induced the phosphorylation of VEGFR2 and its downstream mitogen-activated extracellular regulated kinase (MEK1/2), extracellular regulated protein kinase (ERK1/2) and p38 kinase. CGA reduced high glucose (HG)-induced the activation of microglia BV-2 cells. CGA also reduced HG-induced the increased VEGF expression and hypoxia-inducible factor 1-alpha (HIF-1
February 2018
The minor histocompatibility antigen 1 (HMHA1)/ArhGAP45 is a RacGAP and a novel regulator of endothelial integrity
Publication date: February 2018
Source:Vascular Pharmacology, Volume 101 Author(s): J. Amado-Azevedo, N.R. Reinhard, J. van Bezu, G.P. van Nieuw Amerongen, V.W.M. van Hinsbergh, P.L. Hordijk Endothelial cells line the vasculature and act as gatekeepers that control the passage of plasma, macromolecules and cells from the circulation to the interstitial space. Dysfunction of the endothelial barrier can lead to uncontrolled leak or edema. Vascular leakage is a hallmark of a range of diseases and despite its large impact no specialized therapies are available to prevent or reduce it. RhoGTPases are known key regulators of cellular behavior that are directly involved in the regulation of the endothelial barrier. We recently performed a comprehensive analysis of the effect of all RhoGTPases and their regulators on basal endothelial integrity. In addition to novel positive regulators of endothelial barrier function, we also identified novel negative regulators, of which the ArhGAP45 (also known as HMHA1) was the most significant. We now demonstrate that ArhGAP45 acts as a Rac-GAP (GTPase-Activating Protein) in endothelial cells, which explains its negative effect on endothelial barrier function. Silencing ArhGAP45 not only promotes basal endothelial barrier function, but also increases cellular surface area and induces sprout formation in a 3D-fibrin matrix. Our data further shows that loss of ArhGAP45 promotes migration and shear stress adaptation. In conclusion, we identify ArhGAP45 (HMHA1) as a novel regulator, which contributes to the fine-tuning of the regulation of basal endothelial integrity.

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February 2018
Resveratrol attenuates hyperproliferation of vascular smooth muscle cells from spontaneously hypertensive rats: Role of ROS and ROS-mediated cell signaling
Publication date: February 2018
Source:Vascular Pharmacology, Volume 101 Author(s): Sara Almajdoob, Ekhtear Hossain, Madhu B. Anand-Srivastava Resveratrol, a natural polyphenolic compound has been reported to attenuate angiotensin II -induced vascular smooth muscle cell (VSMC) hypertrophy; however, whether resveratrol could also inhibit hyperproliferation of VSMC from spontaneously hypertensive rats (SHR) is unexplored. The present study investigates the effect of resveratrol on hyperproliferation of VSMC from SHR and the underlying molecular mechanisms responsible for this response. For these studies, aortic VSMC from SHR and Wistar-Kyoto (WKY) rats were used. The proliferation of VSMC was determined by [3H] thymidine incorporation and the levels of proteins were determined by Western blotting. The enhanced proliferation exhibited by VSMC from SHR was attenuated by resveratrol. In addition, resveratrol attenuated the overexpression of cyclin D1, cyclin E, cyclin dependent kinase 4 (Cdk4), Cdk2, phosphorylated retinoblastoma protein (pRb), Gi
February 2018
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Publication date: February 2018
Source:Vascular Pharmacology, Volume 101

Available online 31 January 2018
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Publication date: February 2018
Source:Vascular Pharmacology, Volume 101

Available online 31 January 2018
The quest for endothelial atypical cannabinoid receptor: BKCa channels act as cellular sensors for cannabinoids in in vitro and in situ endothelial cells
Publication date: Available online 31 January 2018
Source:Vascular Pharmacology Author(s): Alexander I. Bondarenko, Olga Panasiuk, Konstantin Drachuk, Fabrizio Montecucco, Karim J. Brandt, Fran
Available online 12 January 2018
A positive feedback loop between IL-1
Available online 12 January 2018
Gliclazide, a KATP channel blocker, inhibits vascular smooth muscle cell proliferation through the CaMKK
Available online 2 January 2018
Hyperglycaemia disrupts conducted vasodilation in the resistance vasculature of db/db mice
Publication date: Available online 12 January 2018
Source:Vascular Pharmacology Author(s): Hamish A.L. Lemmey, Xi Ye, Hong Ding, Chris R. Triggle, Christopher J. Garland, Kim A. Dora Vascular dysfunction in small resistance arteries is observed during chronic elevations in blood glucose. Hyperglycaemia-associated effects on endothelium-dependent vasodilation have been well characterized, but effects on conducted vasodilation in the resistance vasculature are not known. Small mesenteric arteries were isolated from healthy and diabetic db/db mice, which were used as a model of chronic hyperglycaemia. Endothelium-dependent vasodilation via the Gq/11-coupled proteinase activated receptor 2 (PAR2) was stimulated with the selective agonist SLIGRL. The Ca2+-sensitive fluorescent indicator fluo-8 reported changes in endothelial cell (EC) [Ca2+]i, and triple cannulated bifurcating mesenteric arteries were used to study conducted vasodilation. Chronic hyperglycaemia did not affect either EC Ca2+ or local vasodilation to SLIGRL. However, both acute and chronic exposure to high glucose or the mannitol osmotic control attenuated conducted vasodilation to 10
January 2018
Serum adiponectin levels predict acute coronary syndrome (ACS) in patients with severe carotid stenosis
Publication date: Available online 2 January 2018
Source:Vascular Pharmacology Author(s): Luca Liberale, Federico Carbone, Maria Bertolotto, Aldo Bonaventura, Alessandra Vecchi
January 2018
Editorial Board
Publication date: January 2018
Source:Vascular Pharmacology, Volume 100

January 2018
Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases
Publication date: January 2018
Source:Vascular Pharmacology, Volume 100 Author(s): Maria Angela Incalza, Rossella D'Oria, Annalisa Natalicchio, Sebastio Perrini, Luigi Laviola, Francesco Giorgino Reactive oxygen species (ROS) are reactive intermediates of molecular oxygen that act as important second messengers within the cells; however, an imbalance between generation of reactive ROS and antioxidant defense systems represents the primary cause of endothelial dysfunction, leading to vascular damage in both metabolic and atherosclerotic diseases. Endothelial activation is the first alteration observed, and is characterized by an abnormal pro-inflammatory and pro-thrombotic phenotype of the endothelial cells lining the lumen of blood vessels. This ultimately leads to reduced nitric oxide (NO) bioavailability, impairment of the vascular tone and other endothelial phenotypic changes collectively termed endothelial dysfunction(s). This review will focus on the main mechanisms involved in the onset of endothelial dysfunction, with particular focus on inflammation and aberrant ROS production and on their relationship with classical and non-classical cardiovascular risk factors, such as hypertension, metabolic disorders, and aging. Furthermore, new mediators of vascular damage, such as microRNAs, will be discussed. Understanding mechanisms underlying the development of endothelial dysfunction is an important base of knowledge to prevent vascular damage in metabolic and cardiovascular diseases.

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January 2018
Effects of psychopharmacological treatment with antipsychotic drugs on the vascular system
Publication date: January 2018
Source:Vascular Pharmacology, Volume 100 Author(s): Kai G. Kahl, Mechthild Westhoff-Bleck, Tillmann H.C. Kr
January 2018
Regulation and function of endothelial glycocalyx layer in vascular diseases
Publication date: January 2018
Source:Vascular Pharmacology, Volume 100 Author(s): Irina Sieve, Anja K M
January 2018
Axitinib attenuates intraplaque angiogenesis, haemorrhages and plaque destabilization in mice
Publication date: January 2018
Source:Vascular Pharmacology, Volume 100 Author(s): Bieke Van der Veken, Guido R.Y. De Meyer, Wim Martinet Aim An increased density of intraplaque (IP) microvessels in ruptured versus nonruptured human plaques suggests that IP neovascularization has a major causative effect on plaque development and instability. Possibly, vascular endothelial growth factor (VEGF) or other angiogenic factors mediate IP microvessel growth and plaque destabilization. Because apolipoprotein deficient mice with a heterozygous mutation (C1039G+/
January 2018
Reversal effects of low-dose imatinib compared with sunitinib on monocrotaline-induced pulmonary and right ventricular remodeling in rats
Publication date: January 2018
Source:Vascular Pharmacology, Volume 100 Author(s): Zi Ping Leong, Ayumi Okida, Masahi Higuchi, Yoshiaki Yamano, Yoshiaki Hikasa High-dose imatinib reverses cardiopulmonary remodeling but adverse effects limit its clinical use. Efficacy of the multi-kinase inhibitor sunitinib remains questionable. We compared anti-remodeling effects of imatinib with sunitinib on monocrotaline-induced right ventricular (RV) hypertrophy and pulmonary arterial remodeling in rats, focusing on a lower dose. Fourteen days after monocrotaline injection, oral gavage of imatinib (5, 15, or 50mg/kg), sunitinib (0.3, 1, 3, or 10mg/kg), or water for 14days was started. RV hypertrophy and b-type natriuretic peptide mRNA levels were significantly and dose-dependently reduced, much greater in imatinib- than sunitinib-treated groups. Imatinib normalized muscularization of 2050
January 2018
Endothelium-derived contraction in a model of rheumatoid arthritis is mediated via angiotensin II type 1 receptors
Publication date: January 2018
Source:Vascular Pharmacology, Volume 100 Author(s): Kayleigh Hamilton, Lynette Dunning, William R. Ferrell, John C. Lockhart, Andrew MacKenzie A role for endothelium-derived constricting factors (EDCF), and the angiotensin II type 1 receptor (AT1R) pathway, in the vascular impairment found in the rat Freund's complete adjuvant (FCA)-model of rheumatoid arthritis (RA) was examined. FCA arthritis was induced in ratslosartan. Vehicle-treated rats served as controls. Knee-joint swelling and red blood cell (RBC) aggregation were measured as indicators of inflammation and endothelium reactivity assessed by response to acetylcholine (ACh) on aortic rings. Results show that knee-joint swelling and RBC aggregation were elevated in the FCA+vehicle group and restored to control levels in the FCA+losartan-treated animals. ACh-induced relaxation of aortic rings taken from FCA+vehicle animals was significantly impaired compared to vehicle-controls and this vasoreactivity was restored to control levels in the FCA+losartan-treated group. Further examination of aorta from the FCA+vehicle animals revealed an EDCF that was reliant on cyclooxygenase-2 (but not cyclooxygenase-1), generation of superoxide anion generation (but not hydrogen peroxide) and activation of thromboxane-prostanoid receptor. Losartan administration in vivo or ex vivo (to aortic rings) prevented the generation of the EDCF. In summary, this is the first evidence of an EDCF in a model of RA and identifies this mechanism as potentially significant in the cardiovascular disorder associated with the disease.

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January 2018
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Publication date: January 2018
Source:Vascular Pharmacology, Volume 100

Available online 21 December 2017
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Publication date: January 2018
Source:Vascular Pharmacology, Volume 100

Available online 15 December 2017
Evidence for the use of mineralocorticoid receptor antagonists in the treatment of coronary artery disease and post-angioplasty restenosis
Publication date: Available online 21 December 2017
Source:Vascular Pharmacology Author(s): Jochen Dutzmann, Johann Bauersachs, Daniel G. Sedding Mineralocorticoid receptor antagonists (MRAs), such as spironolactone and eplerenone have an established role in the treatment of heart failure. However, many experimental and clinical studies have shown that aldosterone also plays a pivotal role in a variety of other pathophysiological conditions within the cardiovascular system. Aldosterone has been suggested to promote inflammation, endothelial dysfunction and smooth muscle cell hyperplasia during the development of atherosclerosis, thereby promoting the development of coronary artery disease (CAD). Since CAD and subsequent ischemic cardiomyopathy are the major causes of heart failure, it is of major interest, whether pharmacological therapy with MRAs among heart failure patients will also affect the common underlying conditions, namely, atherosclerosis and subsequent coronary vessel narrowing/rarefication. Therefore, in this article, we reviewed and discussed the preclinical and clinical evidence of MRAs for the treatment of acute or chronic vascular remodeling processes, such as atherosclerosis and post-angioplasty restenosis, which determine the progression of CAD and subsequent ischemic cardiomyopathy.

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Available online 13 December 2017
UDP-sugars activate P2Y14 receptors to mediate vasoconstriction of the porcine coronary artery
Publication date: Available online 15 December 2017
Source:Vascular Pharmacology Author(s): Zainab S.B. Abbas, M. Liaque Latif, Natalia Dovlatova, Sue C. Fox, Stan Heptinstall, William R. Dunn, Vera Ralevic Aims UDP-sugars can act as extracellular signalling molecules, but relatively little is known about their cardiovascular actions. The P2Y14 receptor is a Gi/o-coupled receptor which is activated by UDP-glucose and related sugar nucleotides. In this study we sought to investigate whether P2Y14 receptors are functionally expressed in the porcine coronary artery using a selective P2Y14 receptor agonist, MRS2690, and a novel selective P2Y14 receptor antagonist, PPTN (4,7-disubstituted naphthoic acid derivative). Methods and results Isometric tension recordings were used to evaluate the effects of UDP-sugars in porcine isolated coronary artery segments. The effects of the P2 receptor antagonists suramin and PPADS, the P2Y14 receptor antagonist PPTN, and the P2Y6 receptor antagonist MRS2578, were investigated. Measurement of vasodilator-stimulated phosphoprotein (VASP) phosphorylation using flow cytometry was used to assess changes in cAMP levels. UDP-glucose, UDP-glucuronic acid UDP-N-acetylglucosamine (P2Y14 receptor agonists), elicited concentration-dependent contractions in the porcine coronary artery. MRS2690 was a more potent vasoconstrictor than the UDP-sugars. Concentration dependent contractile responses to MRS2690 and UDP-sugars were enhanced in the presence of forskolin (activator of cAMP), where the level of basal tone was maintained by addition of U46619, a thromboxane A2 mimetic. Contractile responses to MRS2690 were blocked by PPTN, but not by MRS2578. Contractile responses to UDP-glucose were also attenuated by PPTN and suramin, but not by MRS2578. Forskolin-induced VASP-phosphorylation was reduced in porcine coronary arteries exposed to UDP-glucose and MRS2690, consistent with P2Y14 receptor coupling to Gi/o proteins and inhibition of adenylyl cyclase activity. Conclusions Our data support a role of UDP-sugars as extracellular signalling molecules and show for the first time that they mediate contraction of porcine coronary arteries via P2Y14 receptors.
December 2017
Periadventitial local drug delivery to target restenosis
Publication date: Available online 13 December 2017
Source:Vascular Pharmacology Author(s): Belay Tesfamariam The adventitia functions as a dynamic compartment for cell trafficking into and out of the artery wall, and communicates with medial and intimal cells. The resident cells in the tunica adventitia play an integral role in the regulation of vessel wall structure, repair, tone, and remodeling. Following injury to the vascular wall, adventitial fibroblasts are activated, which proliferate and differentiate into migratory myofibroblasts, and initiate inflammation through the secretion of soluble factors such as chemokines, cytokines, and adhesion molecules. The secreted factors subsequently promote leukocyte recruitment and extravasation into the media and intima. The adventitia generates reactive oxygen species and growth factors that participate in cell proliferation, migration, and hypertrophy, resulting in intimal thickening. The adventitial vasa vasorum undergoes neovascularization and serves as a port of entry for the delivery of inflammatory cells and resident stem/progenitor cells into the intima, and thus facilitates vascular remodeling. This review highlights the contribution of multilineage cells in the adventitia along with de-differentiated smooth muscle-like cells to the formation of neointimal hyperplasia, and discusses the potential of periadventitial local drug delivery for the prevention of vascular restenosis.

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December 2017
Inside front cover (editorial board members)
Publication date: December 2017
Source:Vascular Pharmacology, Volume 99

December 2017
Graphical abstracts contents listing
Publication date: December 2017
Source:Vascular Pharmacology, Volume 99

December 2017
Update on the role of Pentraxin 3 in atherosclerosis and cardiovascular diseases
Publication date: December 2017
Source:Vascular Pharmacology, Volume 99 Author(s): Matteo Casula, Fabrizio Montecucco, Aldo Bonaventura, Luca Liberale, Alessandra Vecchi
December 2017
Functional diversity of macrophages in vascular biology and disease
Publication date: December 2017
Source:Vascular Pharmacology, Volume 99 Author(s): Inhye Park, Christina Kassiteridi, Claudia Monaco Atherosclerosis is a multifactorial chronic inflammatory disease and is largely responsible for cardiovascular disease, the most common cause of global mortality. The hallmark of atherogenesis is immune activation following lipid accumulation in the arterial wall. In particular, macrophages play a non-redundant role in both the progression and regression of inflammation in the atherosclerotic lesion. Macrophages are remarkably heterogeneous phagocytes that perform versatile functions in health and disease. Their functional diversity in vascular biology is only partially mapped. Targeting macrophages is often highlighted as a therapeutic approach for cancer, metabolic and inflammatory diseases. Future strategies for therapeutic intervention in atherosclerosis may benefit from attempts to reduce local proliferation of pro-inflammatory macrophage subsets or enhance resolution of inflammation. Thus, characterisation of macrophage subsets during atherosclerosis would empower clinical interventions. Therefore, it would be of fundamental importance to understand how pathological factors modulate macrophage activity in order to exploit their use in the treatment of atherosclerosis and other diseases.

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December 2017
Vascular activation of K+ channels and Na+-K+ ATPase activity of estrogen-deficient female rats
Publication date: December 2017
Source:Vascular Pharmacology, Volume 99 Author(s): Rog
December 2017
Protein kinase CK2 inhibition suppresses neointima formation via a proline-rich homeodomain-dependent mechanism
Publication date: December 2017
Source:Vascular Pharmacology, Volume 99 Author(s): K.S. Wadey, B.A. Brown, G.B. Sala-Newby, P.-S. Jayaraman, K. Gaston, S.J. George Neointimal hyperplasia is a product of VSMC replication and consequent accumulation within the blood vessel wall. In this study, we determined whether inhibition of protein kinase CK2 and the resultant stabilisation of proline-rich homeodomain (PRH) could suppress VSMC proliferation. Both silencing and pharmacological inhibition of CK2 with K66 antagonised replication of isolated VSMCs. SiRNA-induced knockdown as well as ectopic overexpression of proline-rich homeodomain indicated that PRH disrupts cell cycle progression. Mutation of CK2 phosphorylation sites Ser163 and Ser177 within the PRH homeodomain enabled prolonged cell cycle arrest by PRH. Concomitant knockdown of PRH and inhibition of CK2 with K66 indicated that the anti-proliferative action of K66 required the presence of PRH. Both K66 and adenovirus-mediated gene transfer of S163C:S177C PRH impaired neointima formation in human saphenous vein organ cultures. Importantly, neither intervention had notable effects on cell cycle progression, cell survival or migration in cultured endothelial cells.

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December 2017
Sub-therapeutic doses of fluvastatin and valsartan are more effective than therapeutic doses in providing beneficial cardiovascular pleiotropic effects in rats: A proof of concept study
Publication date: December 2017
Source:Vascular Pharmacology, Volume 99 Author(s): Miodrag Jani
December 2017
Renal and femoral venous blood flows are regulated by different mechanisms dependent on
December 2017
The influence of DOCA-salt hypertension and chronic administration of the FAAH inhibitor URB597 on KCa2.3/KCa3.1-EDH-type relaxation in rat small mesenteric arteries
Publication date: December 2017
Source:Vascular Pharmacology, Volume 99 Author(s): Monika Kloza, Marta Baranowska-Kuczko, Barbara Malinowska, Olga Karpi
December 2017
Gallic acid attenuates pulmonary fibrosis in a mouse model of transverse aortic contraction-induced heart failure
Publication date: December 2017
Source:Vascular Pharmacology, Volume 99 Author(s): Li Jin, Zhe Hao Piao, Simei Sun, Bin Liu, Yuhee Ryu, Sin Young Choi, Gwi Ran Kim, Hyung-Seok Kim, Hae Jin Kee, Myung Ho Jeong Gallic acid, a trihydroxybenzoic acid found in tea and other plants, attenuates cardiac hypertrophy, fibrosis, and hypertension in animal models. However, the role of gallic acid in heart failure remains unknown. In this study, we show that gallic acid administration prevents heart failure-induced pulmonary fibrosis. Heart failure induced in mice, 8weeks after transverse aortic constriction (TAC) surgery, was confirmed by echocardiography. Treatment for 2weeks with gallic acid but not furosemide prevented cardiac dysfunction in mice. Gallic acid significantly inhibited TAC-induced pathological changes in the lungs, such as increased lung mass, pulmonary fibrosis, and damaged alveolar morphology. It also decreased the expression of fibrosis-related genes, including collagen types I and III, fibronectin, connective tissue growth factor (CTGF), and phosphorylated Smad3. Further, it inhibited the expression of epithelial-mesenchymal transition (EMT)-related genes, such as N-cadherin, vimentin, E-cadherin, SNAI1, and TWIST1. We suggest that gallic acid has therapeutic potential for the treatment of heart failure-induced pulmonary fibrosis.

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Available online 22 November 2017
Corrigendum to Lack of glutathione peroxidase-1 facilitates a pro-inflammatory and activated vascular endothelium [Vasc. Pharmacol. 79 (2016) 3242]
Publication date: December 2017
Source:Vascular Pharmacology, Volume 99 Author(s): Arpeeta Sharma, Derek Yuen, Olivier Huet, Raelene Pickering, Nada Stefanovic, Pascal Bernatchez, Judy B. de Haan
Available online 19 October 2017
Inorganic nitrite and nitrate in cardiovascular therapy: A better alternative to organic nitrates as nitric oxide donors?
Publication date: Available online 22 November 2017
Source:Vascular Pharmacology Author(s): Thomas M

Contribution of lectin-like oxidized low-density lipoprotein receptor-1 and LOX-1 modulating compounds to vascular diseases
Publication date: Available online 19 October 2017
Source:Vascular Pharmacology Author(s): Anja Hofmann, Coy Brunssen, Henning Morawietz The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the major receptor for binding and uptake of oxidized low-density lipoprotein (oxLDL) in endothelial cells. LOX-1 is also expressed in macrophages, smooth muscle cells and platelets. Following internalization of oxLDL, LOX-1 initiates a vicious cycle from activation of pro-inflammatory signaling pathways, thus promoting an increased reactive oxygen species formation and secretion of pro-inflammatory cytokines. LOX-1 plays a pivotal role in the development of endothelial dysfunction, foam cell and advanced lesions formation as well as in myocardial ischemia. Furthermore, it is known that LOX-1 plays a pivotal role in mitochondrial DNA damage, vascular cell apoptosis, and autophagy. A large number of studies provide evidence of a LOX-1
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