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Vascular pharmacology

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https://www.readbyqxmd.com/read/28095860/mouse-models-of-atherosclerosis-a-historical-perspective-and-recent-advances
#1
REVIEW
Yee Ting Lee, Hiu Yu Lin, Yin Wah Fiona Chan, Ka Hou Christien Li, Olivia Tsz Ling To, Bryan P Yan, Tong Liu, Guangping Li, Wing Tak Wong, Wendy Keung, Gary Tse
Atherosclerosis represents a significant cause of morbidity and mortality in both the developed and developing countries. Animal models of atherosclerosis have served as valuable tools for providing insights on its aetiology, pathophysiology and complications. They can be used for invasive interrogation of physiological function and provide a platform for testing the efficacy and safety of different pharmacological therapies. Compared to studies using human subjects, animal models have the advantages of being easier to manage, with controllable diet and environmental risk factors...
January 17, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28093217/abnormal-cd161-immune-cells-and-ror%C3%AE-t-mediated-enhanced-il-17f-expression-in-genetic-hypertension
#2
Madhu V Singh, Michael Z Cicha, Santosh Kumar, David K Meyerholz, Kaikobad Irani, Mark W Chapleau, François M Abboud
BACKGROUND: Hypertension is considered an immunological disorder. However, the role of IL-17 family in genetic hypertension of the spontaneously hypertensive rat (SHR) has not been investigated. OBJECTIVE: We tested the hypothesis that enhanced Th17 programming and IL-17 expression in abundant CD161+ immune cells in SHR represent an abnormal proinflammatory adaptive immune response. Furthermore, we propose that this response is driven by the master regulator RORγt and a nicotinic proinflammatory innate immune response...
January 13, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28091830/physio-pharmacological-investigations-about-the-anti-inflammatory-and-antinociceptive-efficacy-of-limonene-epoxide
#3
Antonia Amanda Cardoso de Almeida, Renan Oliveira Silva, Lucas Antonio Duarte Nicolau, Tarcísio Vieira de Brito, Damião Pergentino de Sousa, André Luiz Dos Reis Barbosa, Rivelilson Mendes de Freitas, Luciano da Silva Lopes, Jand-Venes Rolim Medeiros, Paulo Michel Pinheiro Ferreira
D-limonene epoxidation generates (+)-limonene epoxide, an understudied compound in the pharmacologically point of view. Herein, we investigated the anti-inflammatory and antinociceptive potentialities of (+)-limonene epoxide and suggested a mechanism of action. The anti-inflammatory potential was analyzed using agents to induce paw edema, permeability, and myeloperoxidase (MPO) activity. Pro-inflammatory cytokines and cell migration of peritoneal cells were also assessed. Antinociceptive effects were evaluated by writhing test induced by acetic acid, formalin, and hot plate assays and contribution of opioid pathways...
January 16, 2017: Inflammation
https://www.readbyqxmd.com/read/28089343/assessment-of-microvascular-endothelial-function-in-type-1-diabetes-using-laser-speckle-contrast-imaging
#4
Alessandra S de M Matheus, Eliete Leão Silva Clemente, Maria de Lourdes Guimarães Rodrigues, Débora Cristina Torres Valença, Marília B Gomes
OBJECTIVE: To test whether laser speckle contrast imaging (LSCI) coupled with physiological post-occlusive reactive hyperemia (PORH) and pharmacological iontophoresis of acetylcholine (ACh) as local vasodilator stimuli could distinguish between cutaneous microvascular responses of Type 1 Diabetes (T1DM)'s patients with endothelial dysfunction and that of healthy controls. METHODS: Patients with T1DM aged ≥12years completed a clinical-epidemiological questionnaire...
January 3, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28087726/benefit-of-mineralocorticoid-receptor-antagonism-in-aki-role-of-vascular-smooth-muscle-rac1
#5
Jonatan Barrera-Chimal, Gwennan André-Grégoire, Aurelie Nguyen Dinh Cat, Sebastian M Lechner, Jérôme Cau, Sonia Prince, Peter Kolkhof, Gervaise Loirand, Vincent Sauzeau, Thierry Hauet, Frédéric Jaisser
AKI is a frequent complication in hospitalized patients. Unfortunately, there is no effective pharmacologic approach for treating or preventing AKI. In rodents, mineralocorticoid receptor (MR) antagonism prevents AKI induced by ischemia-reperfusion (IR). We investigated the specific role of vascular MR in mediating AKI induced by IR. We also assessed the protective effect of MR antagonism in IR-induced AKI in the Large White pig, a model of human AKI. In mice, MR deficiency in smooth muscle cells (SMCs) protected against kidney IR injury...
January 13, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28079254/pharmacological-treatment-of-vascular-risk-factors-for-reducing-mortality-and-cardiovascular-events-in-patients-with-abdominal-aortic-aneurysm
#6
REVIEW
Lindsay Robertson, Edmond Atallah, Gerard Stansby
BACKGROUND: Pharmacological prophylaxis has been proven to reduce the risk of cardiovascular events in individuals with atherosclerotic occlusive arterial disease. However, the role of prophylaxis in individuals with abdominal aortic aneurysm (AAA) remains unclear. Several studies have shown that despite successful repair, those people with AAA have a poorer rate of survival than healthy controls. People with AAA have an increased prevalence of coronary heart disease and risk of cardiovascular events...
January 12, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28078981/resilience-to-alzheimer-s-disease-the-role-of-physical-activity
#7
Pedrinolla Anna, Schena Federico, Venturelli Massimo
BACKGROUND: Although Alzheimer's disease (AD) is a neurodegenerative pathology characterized by accumulation of β-amyloid plaques and neurofibrillary tangles at cerebral level, recent studies highlighted that AD might be the result of many altered physiological processes occurring at whole-organism level. The ability to adapt to stressors by "bending" but not "breaking" can be considered as "resilience". Individuals incline to withstand such pathophysiological challenges, can be considered more resilient than those that do not...
January 11, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28075016/modulation-of-long-term-endothelial-barrier-integrity-is-conditional-to-the-cross-talk-between-akt-and-src-signaling
#8
Fei Gao, Harika Sabbineni, Sandeep Artham, Payaningal R Somanath
Although numerous studies have implicated Akt and Src kinases in vascular endothelial growth factor (VEGF) and Angiopoietin-1 (Ang-1)-induced endothelial-barrier regulation, a link between these two pathways has never been demonstrated. We determined the long-term effects of Akt inhibition on Src activity and vice versa, and in turn, on the human microvascular endothelial cell (HMEC) barrier integrity at the basal level, and in response to growth factors. Our data showed that Akt1 gene knockdown increases gap formation in HMEC monolayer at the basal level...
January 11, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28067899/nitric-oxide-mediates-aortic-disease-in-mice-deficient-in-the-metalloprotease-adamts1-and-in-a-mouse-model-of-marfan-syndrome
#9
Jorge Oller, Nerea Méndez-Barbero, E Josue Ruiz, Silvia Villahoz, Marjolijn Renard, Lizet I Canelas, Ana M Briones, Rut Alberca, Noelia Lozano-Vidal, María A Hurlé, Dianna Milewicz, Arturo Evangelista, Mercedes Salaices, J Francisco Nistal, Luis Jesús Jiménez-Borreguero, Julie De Backer, Miguel R Campanero, Juan Miguel Redondo
Heritable thoracic aortic aneurysms and dissections (TAAD), including Marfan syndrome (MFS), currently lack a cure, and causative mutations have been identified for only a fraction of affected families. Here we identify the metalloproteinase ADAMTS1 and inducible nitric oxide synthase (NOS2) as therapeutic targets in individuals with TAAD. We show that Adamts1 is a major mediator of vascular homeostasis, given that genetic haploinsufficiency of Adamts1 in mice causes TAAD similar to MFS. Aortic nitric oxide and Nos2 levels were higher in Adamts1-deficient mice and in a mouse model of MFS (hereafter referred to as MFS mice), and Nos2 inactivation protected both types of mice from aortic pathology...
January 9, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28067791/ligands-of-therapeutic-utility-for-the-liver-x-receptors
#10
REVIEW
Rajesh Komati, Dominick Spadoni, Shilong Zheng, Jayalakshmi Sridhar, Kevin E Riley, Guangdi Wang
Liver X receptors (LXRs) have been increasingly recognized as a potential therapeutic target to treat pathological conditions ranging from vascular and metabolic diseases, neurological degeneration, to cancers that are driven by lipid metabolism. Amidst intensifying efforts to discover ligands that act through LXRs to achieve the sought-after pharmacological outcomes, several lead compounds are already being tested in clinical trials for a variety of disease interventions. While more potent and selective LXR ligands continue to emerge from screening of small molecule libraries, rational design, and empirical medicinal chemistry approaches, challenges remain in minimizing undesirable effects of LXR activation on lipid metabolism...
January 5, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28067284/oleanolic-acid-ameliorates-high-glucose-induced-endothelial-dysfunction-via-ppar%C3%AE-activation
#11
Zihui Zhang, Manli Jiang, Xinya Xie, Haixia Yang, Xinfeng Wang, Lei Xiao, Nanping Wang
Oleanolic acid (3β-hydroxyolean-12-en-28-oic acid, OA) is a pentacyclic triterpenes widely distributed in food, medicinal plants and nutritional supplements. OA exhibits various pharmacological properties, such as hepatoprotective and anti-tumor effects. In this study, we analyzed the effect of OA on endothelial dysfunction induced by high glucose in human vascular endothelial cells (ECs). Western blotting showed that OA attenuated high glucose-reduced nitric production oxide (NO) as well as Akt-Ser(473) and eNOS-Ser(1177) phosphorylation in cultured human umbilical vein ECs (HUVECs)...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28064160/specific-heparanase-inhibition-reverses-glucose-induced-mesothelial-to-mesenchymal-transition
#12
Valentina Masola, Simona Granata, Gloria Bellin, Giovanni Gambaro, Maurizio Onisto, Carlo Rugiu, Antonio Lupo, Gianluigi Zaza
BACKGROUND: Epithelial-to-mesenchymal transition (EMT) of peritoneal mesothelial cells induced by high glucose (HG) levels is a major biological mechanism leading to myofibroblast accumulation in the omentum of patients on peritoneal dialysis (PD). Heparanase (HPSE), an endoglycosidase that cleaves heparan sulfate chains, is involved in the EMT of several cell lines, and may have a major role in this pro-fibrotic process potentially responsible for the failure of dialysis. Its specific inhibition may therefore plausibly minimize this pathological condition...
January 7, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28062494/cellular-repressor-of-e1a-stimulated-genes-is-a-critical-determinant-of-vascular-remodeling-in-response-to-angiotensin-ii
#13
Li Yang, Liu Yanxia, Tian Xiaoxiang, Zhang Yan, Song Haixu, Liu Meili, Zhang Xiaolin, Liu Haiwei, Zhang Jian, Zhang Quanyu, Liu Dan, Peng Chengfei, Yan Chenghui, Han Yaling
OBJECTIVE: Cellular repressor of E1A-stimulated genes (CREG) is a lysosomal glycoprotein implicated in maintaining vascular homeostasis. Here, we have hypothesized that CREG is a critical target of intervention for the prevention of hypertensive vascular remodeling. APPROACH AND RESULTS: CREG gene expression was significantly decreased accompanied by an upregulated expression of angiotensin II (Ang II) in remodeled vascular tissues of high salt-induced Dahl salt-sensitive rats and Ang II-induced mice...
January 5, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28062482/dysregulated-nox4-ubiquitination-contributes-to-redox-imbalance-and-age-related-severity-of-acute-lung-injury
#14
Sunmi Palumbo, Yoon-Joo Shin, Kareem Ahmad, Ankit A Desai, Hector Quijada, Mohamed Mohamed, Adam Knox, Saad Sammani, Brett A Colson, Ting Wang, Joe G N Garcia, Louise Hecker
Acute respiratory distress syndrome (ARDS) is a devastating critical illness disproportionately affecting the elderly population(higher incidence and mortality). The integrity of the lung endothelial cell (EC) monolayer is critical for preservation of lung function. However, mechanisms mediating EC barrier regulation in aging remain unclear. We assessed the severity of acute lung injury (ALI) in young (2 months) and aged (18 months) mice using a two-hit pre-clinical model. Compared to young cohorts, aged mice exhibited increased ALI severity, with greater vascular permeability characterized by elevated albumin influx, levels of bronchoalveolar lavage (BAL) cells (neutrophils) and protein...
January 6, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28061467/cytological-study-on-the-regulation-of-lymphocyte-homing-in-the-chicken-spleen-during-lps-stimulation
#15
Qian Zhang, Yasir Waqas, Ping Yang, Xuejing Sun, Yi Liu, Nisar Ahmed, Bing Chen, Quanfu Li, Lisi Hu, Yufei Huang, Hong Chen, Bing Hu, Qiusheng Chen
The immune function of the chicken spleen depends on its different compartments of red and white pulps, but little is known about the mechanism underlying lymphocyte homing towards the different compartments. In the present study, the role of lymphocyte homing in the chicken spleen was investigated during lipopolysaccharide (LPS) stimulation. Morphological analysis demonstrated the cuboidal endothelial cells of the splenic sheathed capillary facilitated the passage of lymphocyte homing to the chicken spleen...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28060721/dppiv-promotes-endometrial-carcinoma-cell-proliferation-invasion-and-tumorigenesis
#16
Xiaoqing Yang, Xinhua Zhang, Rongrong Wu, Qicheng Huang, Yao Jiang, Jianbing Qin, Feng Yao, Guohua Jin, Yuquan Zhang
Dipeptidyl peptidase IV (DPPIV), also known as CD26, is a 110-kDa cell surface glycoprotein expressed in various tissues. DPPIV reportedly plays a direct role in the progression of several human malignancies. DPPIV specific inhibitors are employed as antidiabetics and could potentially be repurposed to enhance anti-tumor immunotherapies. In the present study, we investigated the correlation between DPPIV expression and tumor progression in endometrial carcinoma (EC). DPPIV overexpression altered cell morphology and stimulated cell proliferation, invasion and tumorigenesis in vitro and in vivo...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28060586/evidence-based-treatment-of-diabetic-macular-edema
#17
Rasha Barham, Hala El Rami, Jennifer K Sun, Paolo S Silva
Diabetes mellitus is a chronic disease that affects 415 million people worldwide. Despite treatment advances, diabetic eye disease remains a leading cause of vision loss worldwide. Diabetic macular edema (DME) is a common cause of vision loss in diabetic patients. The pathophysiology is complex and involves multiple pathways that ultimately lead to central retinal thickening and, if untreated, visual loss. First-line treatment of DME has evolved from focal/grid laser established by the Early Treatment of Diabetic Retinopathy Study (ETDRS) to intravitreous pharmacologic therapy...
2017: Seminars in Ophthalmology
https://www.readbyqxmd.com/read/28056085/vascular-endothelial-over-expression-of-human-soluble-epoxide-hydrolase-tie2-seh-tr-attenuates-coronary-reactive-hyperemia-in-mice-role-of-oxylipins-and-%C3%AF-hydroxylases
#18
Ahmad Hanif, Matthew L Edin, Darryl C Zeldin, Christophe Morisseau, John R Falck, Mohammed A Nayeem
Cytochromes P450 metabolize arachidonic acid (AA) into two vasoactive oxylipins with opposing biologic effects: epoxyeicosatrienoic acids (EETs) and omega-(ω)-terminal hydroxyeicosatetraenoic acids (HETEs). EETs have numerous beneficial physiological effects, including vasodilation and protection against ischemia/reperfusion injury, whereas ω-terminal HETEs induce vasoconstriction and vascular dysfunction. We evaluated the effect of these oxylipins on post-ischemic vasodilation known as coronary reactive hyperemia (CRH)...
2017: PloS One
https://www.readbyqxmd.com/read/28055302/t-type-ca-2-channels-and-autoregulation-of-local-blood-flow
#19
Lars Jørn Jensen, Morten Schak Nielsen, Max Salomonsson, Charlotte Mehlin Sørensen
L-type voltage gated Ca(2+) channels are considered to be the primary source of calcium influx during the myogenic response. However, many vascular beds also express T-type voltage gated Ca(2+) channels. Recent studies suggest that these channels may also play a role in autoregulation. At low pressures (40-80 mm Hg) T-type channels affect myogenic responses in cerebral and mesenteric vascular beds. T-type channels also seem to be involved in skeletal muscle autoregulation. This review discusses the expression and role of T-type voltage gated Ca(2+) channels in the autoregulation of several different vascular beds...
January 5, 2017: Channels
https://www.readbyqxmd.com/read/28055105/restoration-of-perivascular-adipose-tissue-function-in-diet-induced-obese-mice-without-changing-bodyweight
#20
Ning Xia, Sabrina Weisenburger, Egon Koch, Martin Burkart, Gisela Reifenberg, Ulrich Förstermann, Huige Li
BACKGROUND AND PURPOSE: We have recently shown that a reduced function of endothelial nitric oxide synthase (eNOS) in the perivascular adipose tissue (PVAT) contributes crucially to obesity-induced vascular dysfunction in mice. The current study was conducted to test the hypothesis that vascular dysfunction in obesity can be reversed by in vivo improvement of PVAT eNOS activity. EXPERIMENTAL APPROACH: Male C57BL/6 J mice were fed a high-fat diet (HFD) for 22 weeks to induce obesity...
January 5, 2017: British Journal of Pharmacology
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