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https://www.readbyqxmd.com/read/28821752/hybrid-nitric-oxide-donor-and-its-carrier-for-the-treatment-of-peripheral-arterial-diseases
#1
Duong Q Le, Aneetta E Kuriakose, Dat X Nguyen, Kytai T Nguyen, Suchismita Acharya
Nitric oxide (NO) has been known to promote physiological angiogenesis to treat peripheral arterial diseases (PAD) by increasing the vascular endothelial growth factor (VEGF) level in endothelial cells (ECs) and preventing platelet adherence and leukocyte chemotaxis. However, the ongoing ischemic event during peripheral ischemia produces superoxide and diminishes the NO bioavailability by forming toxic peroxynitrite anion. Here we disclose an efficacious hybrid molecule 4-(5-Amino-1,2,3-oxadiazol-3-yl)-2,2,6,6-tetramethyl-1-piperidinol (SA-2) containing both antioxidant and NO donor functionalities that provide a therapeutic level of NO necessary to promote angiogenesis and to protect ECs against hydrogen peroxide-induced oxidative stress...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821433/abcb5-promotes-melanoma-metastasis-through-enhancing-nf-%C3%AE%C2%BAb-p65-protein-stability
#2
Shenghao Wang, Li Tang, Junyu Lin, Zhongliang Shen, Yikun Yao, Wei Wang, Shuai Tao, Chenjian Gu, Jie Ma, Youhua Xie, Yanfeng Liu
Melanoma is the most aggressive type of skin cancer. Melanoma has an extremely poor prognosis because of its high potential for vascular invasion, metastasis and recurrence. The mechanism of melanoma metastasis is not well understood. ATP-binding cassette sub-family B member 5 (ABCB5) plays a key role in melanoma growth. However, it is uncertain what function ABCB5 may exert in melanoma metastasis. In this report, we for the first time demonstrate ABCB5 as a crucial factor that promotes melanoma metastasis...
August 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28820889/altered-fetal-growth-placental-abnormalities-and-stillbirth
#3
Radek Bukowski, Nellie I Hansen, Halit Pinar, Marian Willinger, Uma M Reddy, Corette B Parker, Robert M Silver, Donald J Dudley, Barbara J Stoll, George R Saade, Matthew A Koch, Carol Hogue, Michael W Varner, Deborah L Conway, Donald Coustan, Robert L Goldenberg
BACKGROUND: Worldwide, stillbirth is one of the leading causes of death. Altered fetal growth and placental abnormalities are the strongest and most prevalent known risk factors for stillbirth. The aim of this study was to identify patterns of association between placental abnormalities, fetal growth, and stillbirth. METHODS AND FINDINGS: Population-based case-control study of all stillbirths and a representative sample of live births in 59 hospitals in 5 geographic areas in the U...
2017: PloS One
https://www.readbyqxmd.com/read/28820848/ranibizumab-and-aflibercept-for-the-treatment-of-pigment-epithelial-detachment-in-neovascular-age-related-macular-degeneration-data-from-an-observational-study
#4
Anagha Vaze, Vuong Nguyen, Vincent Daien, Jennifer J Arnold, Stephanie H Young, Chui M Cheung, Ecosse Lamoureux, Mayuri Bhargava, Daniel Barthelmes, Mark C Gillies
PURPOSE: To assess the effect of intravitreal ranibizumab and aflibercept on retinal pigment epithelial detachment (RPED) in patients with neovascular age-related macular degeneration. METHODS: This was a retrospective analysis of data from a prospectively designed and implemented clinical audit. Analysis included change in RPED dimensions and visual acuity in 92/233 treatment-naive eyes with neovascular age-related macular degeneration and RPED 6 months after treatment with either aflibercept or ranibizumab...
August 16, 2017: Retina
https://www.readbyqxmd.com/read/28820609/cardio-pulmonary-interactions-physiologic-basis-and-clinical-applications
#5
Michael R Pinsky
The hemodynamic effects of ventilation can be grouped into three concepts: 1) spontaneous ventilation is exercise; 2) changes in lung volume alter autonomic tone, pulmonary vascular resistance, and can compress the heart in the cardiac fossa; 3) spontaneous inspiratory efforts decrease intrathoracic pressure (ITP) increasing venous return and impeding left ventricular (LV) ejection; whereas positive pressure ventilation decreases venous return and unloads LV ejection. Spontaneous inspiratory efforts may induce acute LV failure and cardiogenic pulmonary edema...
August 18, 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28820443/omega-3-polyunsaturated-fatty-acids-improve-endothelial-dysfunction-in-chronic-renal-failure-role-of-enos-activation-and-of-oxidative-stress
#6
Michela Zanetti, Gianluca Gortan Cappellari, Davide Barbetta, Annamaria Semolic, Rocco Barazzoni
BACKGROUND: Endothelial dysfunction is a key vascular alteration in chronic kidney disease (CKD). Omega 3 (n-3) polyunsaturated fatty acids (PUFA) reduce vascular oxidative stress and inflammation. We investigated whether n-3 PUFA could reverse endothelial dysfunction in CKD by improving endothelial nitric oxide synthase (eNOS) function and oxidative stress. METHODS: 5/6 nephrectomized male Wistar rats (CKD; n = 10) and sham operated animals (SHAM; n = 10) were treated for 6 weeks with standard diet...
August 18, 2017: Nutrients
https://www.readbyqxmd.com/read/28820314/flow-pattern-dependent-endothelial-cell-responses-through-transcriptional-regulation
#7
Hiroyuki Nakajima, Naoki Mochizuki
Blood flow provides endothelial cells (ECs) lining the inside of blood vessels with mechanical stimuli as well as humoral stimuli. Fluid shear stress, the frictional force between flowing blood and ECs, is recognized as an essential mechanical cue for vascular growth, remodeling, and homeostasis. ECs differentially respond to distinct flow patterns. High laminar shear flow leads to inhibition of cell cycle progression and stabilizes vessels, whereas low shear flow or disturbed flow leads to increased turnover of ECs and inflammatory responses of ECs prone to atherogenic...
August 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28820074/exploring-the-cardio-metabolic-relevance-of-t-cadherin-a-pleiotropic-adiponectin-receptor
#8
Jaime Lynn Clark, Carla Gwen Taylor, Peter Zahradka
BACKGROUND AND OBJECTIVE: T cadherin is a unique member of the cadherin family and is primarily expressed in the cardiovascular system. T cadherin has not been abundantly studied, but the studies conducted to date have explored the impact of this protein on health and the function of organs involved in metabolic regulation. METHODS: This article examines the recent knowledge of the ligand partners for T cadherin and the potential contribution(s) of T-cadherin to cardio-metabolic function...
August 18, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/28819713/plasma-growth-differentiation-factor-15-is-a-potential-biomarker-for-pediatric-pulmonary-arterial-hypertension-associated-with-congenital-heart-disease
#9
Gang Li, Yan Li, Xiao-Qiu Tan, Peng Jia, Jian Zhao, Dong Liu, Ting Wang, Bin Liu
We aimed to investigate plasma growth differentiation factor-15 (GDF-15) levels in pediatric pulmonary arterial hypertension secondary to congenital heart disease (PAH-CHD), and assess the association with hemodynamic parameters. Plasma GDF-15 levels were measured in children with PAH-CHD (n = 46) and compared to children with CHD without PAH (n = 39). Normal individuals (n = 30) served as health control group. Plasma GDF-15 levels were significantly elevated in patients with PAH-CHD compared with those with CHD without PAH (median 1415 ng/L, interquartile range [IQR] 926...
August 18, 2017: Pediatric Cardiology
https://www.readbyqxmd.com/read/28819706/generation-of-a-functional-humanized-delta-like-ligand-4-transgenic-mouse-model
#10
John Wiseman, Pernilla Gregersson, Johan Johansson, Kerstin Magnell, Fernanda Pilataxi, Chris Morehouse, Philip Brohawn, Nicholas Holoweckyj, Patrick Strout, Song Cho
Humanized mouse models are important tools in many areas of biological drug development including, within oncology research, the development of antagonistic antibodies that have the potential to block tumor growth by controlling vascularization and are key to the generation of in vivo proof-of-concept efficacy data. However, due to cross reactivity between human antibodies and mouse target such studies regularly require mouse models expressing only the human version of the target molecule. Such humanized knock-in/knock-out, KIKO, models are dependent upon the generation of homozygous mice expressing only the human molecule, compensating for loss of the mouse form...
August 17, 2017: Transgenic Research
https://www.readbyqxmd.com/read/28819545/circulating-mirnas-in-pediatric-pulmonary-hypertension-show-promise-as-biomarkers-of-vascular-function
#11
Vitaly O Kheyfets, Carmen C Sucharov, Uyen Truong, Jamie Dunning, Kendall Hunter, Dunbar Ivy, Shelley Miyamoto, Robin Shandas
BACKGROUND/OBJECTIVES: The objective of this study was to evaluate the utility of circulating miRNAs as biomarkers of vascular function in pediatric pulmonary hypertension. METHOD: Fourteen pediatric pulmonary arterial hypertension patients underwent simultaneous right heart catheterization (RHC) and blood biochemical analysis. Univariate and stepwise multivariate linear regression was used to identify and correlate measures of reactive and resistive afterload with circulating miRNA levels...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28818870/fra-2-negatively-regulates-postnatal-alveolar-septation-by-modulating-myofibroblast-function
#12
Kazuyuki Tsujino, John T Li, Tatsuya Tsukui, Xin Ren, Latifa Bakiri, Erwin F Wagner, Dean Sheppard
Mice that globally over-express the transcription factor, Fos-related antigen-2 (Fra-2), develop extensive pulmonary fibrosis and pulmonary vascular remodeling. To determine if these phenotypes are a consequence of ectopic Fra-2 expression in vascular smooth muscle cells and myofibroblasts, we generated mice that over-express Fra-2 specifically in these cells types (α-SMA-rtTA; tetO-Fra-2). Surprisingly, these mice did not develop vascular remodeling or pulmonary fibrosis, but developed a spontaneous emphysema-like phenotype characterized by alveolar enlargement...
August 17, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28818856/deletion-of-nf-%C3%AE%C2%BAb-rela-in-angiotensin-ii-sensitive-mesenchymal-cells-blocks-aortic-vascular-inflammation-and-abdominal-aortic-aneurysm-formation
#13
Talha Ijaz, Hong Sun, Irina V Pinchuk, Dianna M Milewicz, Ronald G Tilton, Allan R Brasier
OBJECTIVE: Infusion of angiotensin II (Ang II) induces extracellular matrix remodeling and inflammation resulting in abdominal aortic aneurysms (AAAs) in normolipidemic mice. Although Ang II activates mesenchymal cells in the media and adventitia to become fibrogenic, the sentinel role of this mesenchymal population in modulating the inflammatory response and aneurysms is not known. We test the hypothesis that these fibrogenic mesenchymal cells play a critical role in Ang II-induced aortic wall vascular inflammation and AAA formation...
August 17, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28818340/lps-binding-to-hmgb1-promotes-angiogenic-behavior-of-endothelial-cells-through-inhibition-of-p120-and-cd31-via-erk-p38-src-signaling
#14
Zhenguo Liu, Juan Wang, Wu Xing, Yingqiong Peng, Jun Quan, Xuegong Fan
Lipopolysaccharide (LPS) is known to mediate angiogenic effects in endothelial cells. The underlying mechanisms, however, remain largely unknown. In this study, we showed that LPS induced high motility group box protein 1 (HMGB1) secretion in human pulmonary microvascular endothelial cells (HPMECs). Knockdown and overexpression of HMGB1 by adenoviral vectors effectively inhibited and promoted LPS-induced HPMEC migration and capillary-like tube formation, respectively. On the other hand, HMGB1 exerted an inhibitory effect on LPS-suppressed expression of platelet-endothelial cell adhesion molecule (CD31) and p120 catenin (p120); HMGB1 knockdown reversed this effect...
August 9, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28818232/review-of-the-endothelial-pathogenic-mechanism-of-tie2-related-venous-malformation
#15
REVIEW
Zhong Du, JiaWei Zheng, ZhiYuan Zhang, YanAn Wang
BACKGROUND: Venous malformation (VM) is a type of disease involving vascular morphogenesis in humans. Clinically, VM can be sporadic or inherited. TIE2, also known as TEK or HYK, is a member of the receptor tyrosine kinase subfamily and is highly conserved among species. In 1996, an arginine-to-tryptophan substitution at position 849 (R849W) in TIE2 was found to induce hereditary VM. Additional alterations in TIE2 involved in the pathogenesis of inherited or sporadic VM have since been reported...
September 2017: Journal of Vascular Surgery. Venous and Lymphatic Disorders
https://www.readbyqxmd.com/read/28818116/distinct-white-matter-microstructural-abnormalities-and-extracellular-water-increases-relate-to-cognitive-impairment-in-alzheimer-s-disease-with-and-without-cerebrovascular-disease
#16
Fang Ji, Ofer Pasternak, Siwei Liu, Yng Miin Loke, Boon Linn Choo, Saima Hilal, Xin Xu, Mohammad Kamran Ikram, Narayanaswamy Venketasubramanian, Christopher Li-Hsian Chen, Juan Zhou
BACKGROUND: Mixed vascular and neurodegenerative dementia, such as Alzheimer's disease (AD) with concomitant cerebrovascular disease, has emerged as the leading cause of age-related cognitive impairment. The brain white matter (WM) microstructural changes in neurodegeneration well-documented by diffusion tensor imaging (DTI) can originate from brain tissue or extracellular free water changes. The differential microstructural and free water changes in AD with and without cerebrovascular disease, especially in normal-appearing WM, remain largely unknown...
August 17, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28817716/endothelial-dysfunction-in-renal-arcuate-arteries-of-obese-zucker-rats-the-roles-of-nitric-oxide-endothelium-derived-hyperpolarizing-factors-and-calcium-activated-k-channels
#17
Dandan Yin, Qianchen Wang, Xun Zhou, Ying Li
The roles of nitric oxide (NO), endothelium-derived hyperpolarizing factors (EDHF), and calcium-activated K+ (KCa) channels in diabetes-associated endothelial dysfunction of small renal arteries are not clear. The present study investigated acetylcholine (ACh)-induced vasorelaxation of renal arcuate arteries from obese Zucker (OZ) rats at different diabetes durations, and the relative contribution of NO, EDHF, and KCa channels to the endothelial dysfunction. OZ rats of 7 weeks (prediabetic stage), 12 weeks (early diabetic stage), and 20 weeks (late diabetic stage), and time-matched lean control rats, were studied...
2017: PloS One
https://www.readbyqxmd.com/read/28817706/hiv-infection-antiretroviral-therapy-and-measures-of-endothelial-function-inflammation-metabolism-and-oxidative-stress
#18
Andrew Dysangco, Ziyue Liu, James H Stein, Michael P Dubé, Samir K Gupta
BACKGROUND: HIV-infected patients have an increased risk of cardiovascular disease (CVD). Impaired endothelial function is an early risk factor for CVD in the general population. It is presumed that HIV infection is associated with impaired endothelial function, but results have been inconsistent. OBJECTIVES: Our objectives were to determine the relationships between HIV infection, virologic suppression with antiretroviral therapy (ART), in vivo measures of conduit artery and microvascular endothelial function, and circulating biomarkers of pathways associated with CVD...
2017: PloS One
https://www.readbyqxmd.com/read/28817646/genetic-dissection-of-endothelial-transcriptional-activity-of-zebrafish-aryl-hydrocarbon-receptors-ahrs
#19
Wade W Sugden, Roberto C Leonardo-Mendonça, Darío Acuña-Castroviejo, Arndt F Siekmann
The aryl hydrocarbon receptor (AHR) is a basic helix-loop-helix transcription factor conserved across phyla from flies to humans. Activated by a number of endogenous ligands and environmental toxins, studies on AHR function and gene regulation have largely focused on a toxicological perspective relating to aromatic hydrocarbons generated by human activities and the often-deleterious effects of exposure on vertebrates mediated by AHR activation. A growing body of work has highlighted the importance of AHR in physiologic processes, including immune cell differentiation and vascular patterning...
2017: PloS One
https://www.readbyqxmd.com/read/28817509/high-intensity-exercise-enhances-conduit-artery-vascular-function-in-older-adults
#20
Erika Iwamoto, Josh M Bock, Darren P Casey
PURPOSE: Modulation of vascular function follows an exercise intensity-dependent pattern in young adults. This study aimed to investigate the potential intensity-dependent effects of an acute bout of exercise on conduit and resistance artery function in healthy older adults. METHODS: Eleven healthy older adults (5 males/6 females, 66±1 years) completed 30 minutes of recumbent cycling at 50-55% (low-intensity) and 75-80% (high-intensity) of their age-predicted maximal heart rate on two separate study visits...
August 16, 2017: Medicine and Science in Sports and Exercise
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