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https://www.readbyqxmd.com/read/28075016/modulation-of-long-term-endothelial-barrier-integrity-is-conditional-to-the-cross-talk-between-akt-and-src-signaling
#1
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/28074024/whole-genome-sequencing-of-invasion-resistant-cells-identifies-laminin-%C3%AE-2-as-a-host-factor-for-bacterial-invasion
#2
Xander M van Wijk, Simon Döhrmann, Björn M Hallström, Shangzhong Li, Bjørn G Voldborg, Brandon X Meng, Karen K McKee, Toin H van Kuppevelt, Peter D Yurchenco, Bernhard O Palsson, Nathan E Lewis, Victor Nizet, Jeffrey D Esko
: To understand the role of glycosaminoglycans in bacterial cellular invasion, xylosyltransferase-deficient mutants of Chinese hamster ovary (CHO) cells were created using clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR-associated gene 9 (CRISPR-cas9) gene targeting. When these mutants were compared to the pgsA745 cell line, a CHO xylosyltransferase mutant generated previously using chemical mutagenesis, an unexpected result was obtained. Bacterial invasion of pgsA745 cells by group B Streptococcus (GBS), group A Streptococcus, and Staphylococcus aureus was markedly reduced compared to the invasion of wild-type cells, but newly generated CRISPR-cas9 mutants were only resistant to GBS...
January 10, 2017: MBio
https://www.readbyqxmd.com/read/28072480/free-fatty-acids-induce-autophagy-and-lox-1-upregulation-in-cultured-aortic-vascular-smooth-muscle-cells
#3
Cheng-I Cheng, Yueh-Hong Lee, Po-Han Chen, Yu-Chun Lin, Ming-Huei Chou, Ying-Hsien Kao
Elevation of free fatty acids (FFAs) is known to affect microvascular function and contribute to obesity-associated insulin resistance, hypertension, and microangiopathy. Proliferative and synthetic vascular smooth muscle cells (VSMCs) increase intimal thickness and destabilize atheromatous plaques. This study aimed to investigate whether saturated palmitic acid (PA) and monounsaturated oleic acid (OA) modulate autophagy activity, cell proliferation, and vascular tissue remodeling in an aortic VSMC cell line...
November 5, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28063459/cardiac-remodeling-following-reperfused-acute-myocardial-infarction-is-linked-to-the-concomitant-evolution-of-vascular-function-as-assessed-by-cardiovascular-magnetic-resonance
#4
Olivier Huttin, Damien Mandry, Romain Eschalier, Lin Zhang, Emilien Micard, Freddy Odille, Marine Beaumont, Renaud Fay, Jacques Felblinger, Edoardo Camenzind, Faïez Zannad, Nicolas Girerd, Pierre Y Marie
BACKGROUND: Left ventricular (LV) remodeling following acute myocardial infarction (MI) is difficult to predict at an individual level although a possible interfering role of vascular function has yet to be considered to date. This study aimed to determine the extent to which this LV remodeling is influenced by the concomitant evolution of vascular function and LV loading conditions, as assessed by phase-contrast Cardiovascular Magnetic Resonance (CMR) of the ascending aorta. METHODS: CMR was performed in 121 patients, 2-4 days after reperfusion of a first ST-segment elevation myocardial infarction and 6 months thereafter...
January 4, 2017: Journal of Cardiovascular Magnetic Resonance
https://www.readbyqxmd.com/read/28063233/establishment-of-a-new-conditionally-immortalized-human-skeletal-muscle-microvascular-endothelial-cell-line
#5
Hironori Sano, Yasuteru Sano, Eri Ishiguchi, Fumitaka Shimizu, Masatoshi Omoto, Toshihiko Maeda, Hideaki Nishihara, Yukio Takeshita, Shiori Takahashi, Mariko Oishi, Takashi Kanda
In skeletal muscle, the capillaries have tight junctions (TJs) that are structurally similar to those in the blood-brain barrier (BBB) and blood-nerve barrier (BNB). Although many findings have been clarified in the territory of BBB and BNB, few have so far examined the TJs of capillaries in the skeletal muscle. In addition, no in vitro human skeletal muscle microvasculature models have been reported thus far. We newly established a new human skeletal muscle microvascular endothelial cell (HSMMEC) line. HSMMECs were isolated from human skeletal muscle and were infected with retroviruses harboring temperature-sensitive SV40 T antigen and telomerase genes...
January 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28062999/relationship-between-increased-carotid-artery-stiffness-and-idiopathic-subjective-tinnitus
#6
C Bayraktar, S Taşolar
Tinnitus is defined as perception of sound with no external stimulus, and can separate into pulsatile and non-pulsatile types. Arterial stiffness is a parameter that can predict the cardiovascular event and associated with incidence of stroke. It has been shown that increased arterial stiffness may lead to microvascular damage in brain. Our aim was to assess the arterial stiffness of the carotid system in the development and severity of idiopathic subjective tinnitus. Forty subjective tinnitus patients and 40 age- and sex-matched controls were enrolled in the study...
January 6, 2017: European Archives of Oto-rhino-laryngology
https://www.readbyqxmd.com/read/28062940/vitamin-d-and-diabetes-mellitus-causal-or-casual-association
#7
REVIEW
M Grammatiki, E Rapti, S Karras, R A Ajjan, Kalliopi Kotsa
The incidence of both type 2 and type 1 diabetes mellitus has been increasing worldwide. Vitamin D deficiency, or the awareness of its prevalence, has also been increasing. Vitamin D may have a role in the pathogenic mechanisms predisposing to type 2 diabetes by modulating insulin resistance and/or pancreatic β-cell function. Vitamin D status or elements involved in its activation or transport may also be involved in the development of type 1 diabetes mellitus through immunomodulatory role . Based on these observations a potential association between vitamin D and diabetes has been hypothesized...
January 7, 2017: Reviews in Endocrine & Metabolic Disorders
https://www.readbyqxmd.com/read/28060303/an-in-vitro-model-of-the-blood-brain-barrier-using-impedance-spectroscopy-a-focus-on-t-cell-endothelial-cell-interaction
#8
Ivan Kuzmanov, Alexander M Herrmann, Hans-Joachim Galla, Sven G Meuth, Heinz Wiendl, Luisa Klotz
Breakdown of the blood-brain barrier (BBB) is a critical step in the development of autoimmune diseases such as multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). This process is characterized by the transmigration of activated T cells across brain endothelial cells (ECs), the main constituents of the BBB. However, the consequences on brain EC function upon interaction with such T cells are largely unknown. Here we describe an assay that allows for the evaluation of primary mouse brain microvascular EC (MBMEC) function and barrier integrity during the interaction with T cells over time...
December 8, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28052873/path-of-translational-discovery-of-urological-complications-of-obesity-and-diabetes-ucod
#9
Firouz Daneshgari, Guiming Liu, Ann T Hanna-Mitchell
Diabetes Mellitus (DM) is a prevalent chronic disease. Type 1 diabetes mellitus (T1DM) is a metabolic disorder that is characterized by hyperglycemia in the context of absolute lack of insulin; whereas type 2 diabetes mellitus (T2DM) is due to insulin resistance-related relative insulin deficiency. Obesity is an established risk factor for T2DM. In comparison with T1DM, T2DM is more complex. The natural history of T2DM in most patients typically involves a course of obesity to impaired glucose tolerance, to insulin resistance and hyperglycemia...
January 4, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28042341/anti-angiogenic-nanotherapy-inhibits-airway-remodeling-and-hyper-responsiveness-of-dust-mite-triggered-asthma-in-the-brown-norway-rat
#10
Gregory M Lanza, John Jenkins, Anne H Schmieder, Aigul Moldobaeva, Grace Cui, Huiying Zhang, Xiaoxia Yang, Qiong Zhong, Jochen Keupp, Ismail Sergin, Krishna S Paranandi, Lindsey Eldridge, John S Allen, Todd Williams, Michael J Scott, Babak Razani, Elizabeth M Wagner
Although angiogenesis is a hallmark feature of asthmatic inflammatory responses, therapeutic anti-angiogenesis interventions have received little attention. Objective: Assess the effectiveness of anti-angiogenic Sn2 lipase-labile prodrugs delivered via αvβ3-micellar nanotherapy to suppress microvascular expansion, bronchial remodeling, and airway hyper-responsiveness in Brown Norway rats exposed to serial house dust mite (HDM) inhalation challenges. Results: Anti-neovascular effectiveness of αvβ3-mixed micelles incorporating docetaxel-prodrug (Dxtl-PD) or fumagillin-prodrug (Fum-PD) were shown to robustly suppress neovascular expansion (p<0...
2017: Theranostics
https://www.readbyqxmd.com/read/28035003/a-quininib-analogue-and-cysteinyl-leukotreine-receptor-antagonist-inhibits-vegf-independent-angiogenesis-and-exerts-an-additive-anti-angiogenic-response-with-bevacizumab
#11
Clare T Butler, Alison L Reynolds, Miriam Tosetto, Eugene T Dillon, Patrick Guiry, Gerard Cagney, Jacintha O'Sullivan, Breand Aacuten N Kennedy
Excess blood vessel growth contributes to the pathology of metastatic cancers and age-related retinopathies. Despite development of improved treatments, these conditions are associated with high economic costs and drug resistance. Bevacizumab (Avastin®), a monoclonal antibody against vascular endothelial growth factor (VEGF) is used clinically to treat certain types of metastatic cancers. Unfortunately, many patients do not respond or inevitably become resistant to bevacizumab, highlighting the need for more effective anti-angiogenic drugs with novel mechanisms of action...
December 29, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28032429/under-treatment-of-type-2-diabetes-causes-and-outcomes-of-clinical-inertia
#12
REVIEW
Clifford J Bailey
AIMS: To assess the impact of clinical inertia on type 2 diabetes (T2D) care. METHODS: PubMed database search from January 2000 until December 2015. RESULTS: Clinical inertia, defined as resistance to initiate or intensify treatment in a patient not at the evidence-based glycated haemoglobin goal, is conservatively estimated to occur in at least 25% of patients with T2D. Consequently, many patients with diagnosed and treated T2D experience extended periods, in some cases years, of ineffectively controlled hyperglycaemia, potentially causing serious microvascular and macrovascular harm...
December 2016: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/28025032/the-metabolic-syndrome-and-chronic-kidney-disease
#13
REVIEW
Xin Zhang, Lilach O Lerman
The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors including insulin resistance (IR), dyslipidemia, and hypertension, which may also foster development of chronic kidney disease. The mechanisms of MetS-induced kidney disease are not fully understood. The purpose of this review is to summarize recent discoveries regarding the impact of MetS on the kidney, particularly on the renal microvasculature and cellular mitochondria. Fundamental manifestations of MetS include IR and adipose tissue expansion, the latter promoting chronic inflammation and oxidative stress that exacerbate IR...
December 9, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28017224/hemorrhagic-transformation-and-cerebral-edema-in-acute-ischemic-stroke-link-to-cerebral-autoregulation
#14
Pedro Castro, Elsa Azevedo, Jorge Serrador, Isabel Rocha, Farzaneh Sorond
BACKGROUND: Hemorrhagic transformation and cerebral edema are feared complications of acute ischemic stroke but mechanisms are poorly understood and reliable early markers are lacking. Early assessment of cerebrovascular hemodynamics may advance our knowledge in both areas. We examined the relationship between dynamic cerebral autoregulation (CA) in the early hours post ischemia, and the risk of developing hemorrhagic transformation and cerebral edema at 24h post stroke METHODS: We prospectively enrolled 46 patients from our center with acute ischemic stroke in the middle cerebral artery territory...
January 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28007742/invasive-minimal-microvascular-resistance-is-a-new-index-to-assess-microcirculatory-function-independent-of-obstructive-coronary-artery-disease
#15
Guus A de Waard, Sukhjinder S Nijjer, Martijn A van Lavieren, Nina W van der Hoeven, Ricardo Petraco, Tim P van de Hoef, Mauro Echavarría-Pinto, Sayan Sen, Peter M van de Ven, Paul Knaapen, Javier Escaned, Jan J Piek, Justin E Davies, Niels van Royen
BACKGROUND: Coronary microcirculatory dysfunction portends a poor cardiovascular outcome. Invasive assessment of microcirculatory dysfunction by coronary flow reserve (CFR) and hyperemic microvascular resistance (HMR) is affected by coronary artery disease (CAD). In this study we propose minimal microvascular resistance (mMR) as a new measure of microcirculatory dysfunction and aim to determine whether mMR is influenced by CAD. METHODS AND RESULTS: We obtained 482 simultaneous measurements of intracoronary Doppler flow velocity and pressure...
December 22, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27994454/the-role-of-the-intestinal-microvasculature-in-inflammatory-bowel-disease-studies-with-a-modified-caco-2-model-including-endothelial-cells-resembling-the-intestinal-barrier-in-vitro
#16
Jennifer Y Kasper, Maria Iris Hermanns, Christian Cavelius, Annette Kraegeloh, Thomas Jung, Rolf Danzebrink, Ronald E Unger, Charles James Kirkpatrick
The microvascular endothelium of the gut barrier plays a crucial role during inflammation in inflammatory bowel disease. We have modified a commonly used intestinal cell model based on the Caco-2 cells by adding microvascular endothelial cells (ISO-HAS-1). Transwell filters were used with intestinal barrier-forming Caco-2 cells on top and the ISO-HAS-1 on the bottom of the filter. The goal was to determine whether this coculture mimics the in vivo situation more closely, and whether the model is suitable to evaluate interactions of, for example, prospective nanosized drug vehicles or contrast agents with this coculture in a physiological and inflamed state as it would occur in inflammatory bowel disease...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27988872/insulin-resistance-and-neurodegeneration-progress-towards-the-development-of-new-therapeutics-for-alzheimer-s-disease
#17
REVIEW
Suzanne M de la Monte
Alzheimer's disease (AD) should be regarded as a degenerative metabolic disease caused by brain insulin resistance and deficiency, and overlapping with the molecular, biochemical, pathophysiological, and metabolic dysfunctions in diabetes mellitus, non-alcoholic fatty liver disease, and metabolic syndrome. Although most of the diagnostic and therapeutic approaches over the past several decades have focused on amyloid-beta (Aβ42) and aberrantly phosphorylated tau, which could be caused by consequences of brain insulin resistance, the broader array of pathologies including white matter atrophy with loss of myelinated fibrils and leukoaraiosis, non-Aβ42 microvascular disease, dysregulated lipid metabolism, mitochondrial dysfunction, astrocytic gliosis, neuro-inflammation, and loss of synapses vis-à-vis growth of dystrophic neurites, is not readily accounted for by Aβ42 accumulations, but could be explained by dysregulated insulin/IGF-1 signaling with attendant impairments in signal transduction and gene expression...
December 17, 2016: Drugs
https://www.readbyqxmd.com/read/27988246/identification-of-neuronal-and-angiogenic-growth-factors-in-an-in-vitro-blood-brain-barrier-model-system-relevance-in-barrier-integrity-and-tight-junction-formation-and-complexity
#18
Christian Freese, Sanshiro Hanada, Petra Fallier-Becker, C James Kirkpatrick, Ronald E Unger
We previously demonstrated that the co-cultivation of endothelial cells with neural cells resulted in an improved integrity of the in vitro blood-brain barrier (BBB), and that this model could be useful to evaluate the transport properties of potential central nervous system disease drugs through the microvascular brain endothelial. In this study we have used real-time PCR, fluorescent microscopy, protein arrays and enzyme-linked immunosorbent assays to determine which neural- and endothelial cell-derived factors are produced in the co-culture and improve the integrity of the BBB...
December 15, 2016: Microvascular Research
https://www.readbyqxmd.com/read/27987530/obesity-insulin-resistance-and-microvascular-adaptation
#19
Jefferson C Frisbee
Two of the primary risk factors for the progressive evolution of cardiovascular disease are obesity and impaired glycemic control - including both insulin resistance and overt type 2 diabetes mellitus, leading to increased research emphasis on these conditions, their mechanistic bases and their health outcomes. This Special Topics Issue of the journal Microcirculation summarizes a symposium at the recent Joint Meeting of the American Physiological Society and the Physiological Society, held in Dublin, Ireland on July 30, 2016...
December 17, 2016: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/27974731/egb-761-protects-cardiac-microvascular-endothelial-cells-against-hypoxia-reoxygenation-injury-and-exerts-inhibitory-effect-on-atm-pathway
#20
Chao Zhang, Deng-Feng Wang, Zhuang Zhang, Dong Han, Kan Yang
Ginkgo biloba extract (EGb 761) has been widely clinically used to reduce myocardial ischemia reperfusion injury (MIRI). Microvascular endothelial cells (MVECs) may be a proper cellular model in vitro for the effect and mechanism study against MIRI. However, the effect of EGb 761 on MVECs resisting hypoxia/reoxygenation (H/R) injury is little reported. In this study, H/R-injuried MVECs were treated with EGb 761, then cell viability, apoptosis, ROS production, SOD activity, caspase-3 activity, and the protein level of ATM, γ-H2AX, p53, Bax were measured...
December 14, 2016: Journal of Microbiology and Biotechnology
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