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endothelial permeability

Qilong Feng, Christian J Stork, Sulei Xu, Dong Yuan, Xinghai Xia, Kyle B LaPenna, Ge Guo, Haoyu Sun, Li-Chong Xu, Christopher Siedlecki, Kathleen Brundage, Nate Sheaffer, Todd D Schell, Pingnian He
In various cardiovascular diseases, microparticles (MPs), the membrane-derived vesicles released during cell activation, are markedly increased in the circulation. These MPs have been recognized to play diverse roles in the regulation of cellular functions. However, current knowledge of MP function has been largely concluded from in vitro studies. The precise impact of disease-induced MPs on vascular inflammation and disease progression remain obscure. In this study we investigated the biogenesis, profile, and functional roles of circulating MPs using a streptozotocin-induced diabetic rat model with well-characterized microvascular functions...
December 11, 2018: Journal of Physiology
Patrizia Leone, Giuseppe Di Lernia, Antonio Giovanni Solimando, Sebastiano Cicco, Ilaria Saltarella, Aurelia Lamanuzzi, Roberto Ria, Maria Antonia Frassanito, Maurilio Ponzoni, Paolo Ditonno, Franco Dammacco, Vito Racanelli, Angelo Vacca
Endothelial cells (EC) line the bone marrow microvasculature and are in close contact with CD8+ T cells that come and go across the permeable capillaries. Because of these intimate interactions, we investigated the capacity of EC to act as antigen-presenting cells (APC) and modulate CD8+ T cell activation and proliferation in bone marrow of patients with multiple myeloma (MM) and monoclonal gammopathy of undetermined significance. We found that EC from MM patients show a phenotype of semi-professional APC given that they express low levels of the co-stimulatory molecules CD40, CD80 and CD86, and of the inducible co-stimulator ligand (ICOSL)...
2019: Oncoimmunology
Shi Li, Mingmei Zhong, Yuan Yuan, Lin Zhang
Angiopoietin-2 (Ang-2) is a Tie-2 ligand that destabilizes vascular structures, enhances vascular permeability and induces vascular regression and endothelial cell apoptosis. Although there is evidence for the involvement of the Ang/Tie2 axis in acute lung injury (ALI), the underlying mechanisms involved in Ang-2-induced cell apoptosis are not well understood. In this study, whether Ang-2 contributes to microvascular endothelial cell injury and mediates lipopolysaccharide (LPS)-induced endothelial cell apoptosis and its associated signaling pathways was investigated...
December 2018: Experimental and Therapeutic Medicine
Chun Tang, Shengyu Tan, Yiqing Zhang, Lini Dong, Yan Xu
High glucose (HG) induces oxidative injury to cultured human umbilical vein endothelial cells (HUVECs). Recent studies have discovered 4-octyl itaconate (OI) as a novel and cell permeable Nrf2 (nuclear-factor-E2-related factor 2) activator. Its potential activity in HG-treated HUVECs was tested here. In HUVECs OI disrupted Keap1-Nrf2 association, causing Nrf2 protein accumulation and nuclear translocation, as well as transcription and expression of Nrf2-ARE-dependent genes, including HO1, NQO1 and GCLM. Significantly, pretreatment with OI potently inhibited HG (40 mM glucose)-induced death and apoptosis of HUVECs...
December 10, 2018: Biochemical and Biophysical Research Communications
Valerio Ciccone, Erika Terzuoli, Sandra Donnini, Antonio Giachetti, Lucia Morbidelli, Marina Ziche
BACKGROUND: Aldehyde dehydrogenase 1A1 (ALDH1A1), a member of aldehyde dehydrogenase family, is a marker of stemness in breast cancer. During tumor progression cancer stem cells (CSCs) have been reported to secrete angiogenic factors to orchestrate the formation of pathological angiogenesis. This vasculature can represent the source of self-renewal of CSCs and the route for further tumor spreading. The aim of the present study has been to assess whether ALDH1A1 controls the output of angiogenic factors in breast cancer cells and regulates tumor angiogenesis in a panel of in vitro and in vivo models...
December 12, 2018: Journal of Experimental & Clinical Cancer Research: CR
G Nannelli, E Terzuoli, V Giorgio, S Donnini, P Lupetti, A Giachetti, P Bernardi, M Ziche
Endothelial cells (ECs) are dynamic cells that turn from growth into senescence, the latter being associated with cellular dysfunction, altered metabolism, and age-related cardiovascular diseases. Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme metabolizing acetaldehyde and other toxic aldehydes, such as 4-hydroxynonenal (4-HNE). In conditions in which lipid peroxidation products and reactive oxygen species (ROS) are accumulated, ECs become dysfunctional and significantly contribute to the progression of vascular-dependent diseases...
2018: Oxidative Medicine and Cellular Longevity
Gerard A Rodrigues, Matthew Mason, Lori-Ann Christie, Candice Hansen, Lisa M Hernandez, James Burke, Keith A Luhrs, Thomas C Hohman
Purpose: DARPin molecules are a novel class of small proteins that contain engineered ankyrin repeat domain(s) and bind to target proteins with high specificity and affinity. Abicipar-pegol (abicipar), a DARPin molecule targeting vascular endothelial growth factor-A (VEGF-A), is currently under evaluation in patients with age-related macular degeneration. The pharmacodynamic properties of abicipar were characterized using in vivo and in vitro assays. Methods: The binding affinity of abicipar was assessed using a kinetic exclusion assay (KinExA)...
December 3, 2018: Investigative Ophthalmology & Visual Science
Ciro De Luca, Anna Maria Colangelo, Lilia Alberghina, Michele Papa
Coagulation and the immune system interact in several physiological and pathological conditions, including tissue repair, host defense, and homeostatic maintenance. This network plays a key role in diseases of the central nervous system (CNS) by involving several cells (CNS resident cells, platelets, endothelium, and leukocytes) and molecular pathways (protease activity, complement factors, platelet granule content). Endothelial damage prompts platelet activation and the coagulation cascade as the first physiological step to support the rescue of damaged tissues, a flawed rescuing system ultimately producing neuroinflammation...
2018: Frontiers in Cellular Neuroscience
Yongzhi Qiu, Byungwook Ahn, Yumiko Sakurai, Caroline Hansen, Reginald Tran, Patrice N Mimche, Robert Mannino, Jordan C Ciciliano, Tracey J Lamb, Clinton H Joiner, Solomon F Ofori-Acquah, Wilbur A Lam
Alterations in the mechanical properties of erythrocytes occurring in inflammatory and hematologic disorders such as sickle cell disease (SCD) and malaria often lead to increased endothelial permeability, haemolysis, and microvascular obstruction. However, the associations among these pathological phenomena remain unknown. Here, we report a perfusable, endothelialized microvasculature-on-a-chip featuring an interpenetrating-polymer-network hydrogel that recapitulates the stiffness of blood-vessel intima, basement membrane self-deposition and self-healing endothelial barrier function for longer than 1 month...
2018: Nature Biomedical Engineering
David J Lundy, Keng-Jung Lee, I-Chia Peng, Chia-Hsin Hsu, Jen-Hao Lin, Kun-Hung Chen, Yu-Wen Tien, Patrick C H Hsieh
The blood brain barrier (BBB) selectively controls the passage of endogenous and exogenous molecules between systemic circulation and the brain parenchyma. Nano-carrier based drugs such as liposomes and nanoparticles are an attractive prospect for cancer therapy since they can carry a drug payload and be modified to improve targeting and retention at the desired site. However, the BBB prevents most therapeutic drugs from entering the brain, including physically restricting the passage of liposomes and nanoparticles...
December 11, 2018: ACS Nano
Timothée Naret, Ilhem Khelifi, Olivier Provot, Jérôme Bignon, Helene Levaique, Joëlle Dubois, Martin Souce, Athena Kasselouri, Alain Deroussent, Angelo Paci, Paloma F Varela, Benoît Gigant, Mouad Alami, Abdallah Hamze
We report the synthesis, metabolism and biological evaluation of a series of 17 novel heterocyclic derivatives of isoCombretastatin-A4 and their structure-activity relationship. Among these derivatives, the most active compound 4f inhibited the growth of a panel of seven cancer cell lines with an IC50 in the low nanomolar range. In addition, 4f showed interesting activity against CA-4-resistant colon carcinoma cells and multidrug-resistant leukemia cells. It also induced G2/M cell cycle arrest. Structural data indicated binding of 4f to the colchicine site of tubulin, likely preventing the curved-to-straight tubulin structural changes that occur during microtubule assembly...
December 10, 2018: Journal of Medicinal Chemistry
Francisco Rodríguez-Esparragón, Silvia Marrero-Robayna, Fayna González-Cabrera, Yaridé Hernández-Trujillo, Nisa Buset-Ríos, José Carlos Rodríguez-Pérez, Nicanor Vega-Díaz
Background: We have compared the effects of conventional lactate-based peritoneal dialysis fluid (CPDF) with respect to bicarbonate/lactate-based fluid on peritoneal ultrafiltration (UF) and peritoneal permeability, and on variations on gene expression in cells isolated from effluents of patients' peritoneal bags. Methods: This was a non-randomized sequential prospective study including all incident peritoneal dialysis (PD) patients ( n  = 40) recruited in our centre...
December 2018: Clinical Kidney Journal
Chaoling Dong, Eroboghene E Ubogu
The human blood-nerve barrier (BNB) formed by endoneurial microvascular endothelial cells, serves to maintain the internal microenvironment in peripheral nerves required for normal axonal signal transduction to and from the central nervous system. The mechanisms of human BNB formation in health and disease are not fully elucidated. Prior work established a sufficient role for glial-derived neurotrophic factor (GDNF) in enhancing human BNB biophysical properties following serum withdrawal in vitro via RET-tyrosine kinase-dependent cytoskeletal remodeling...
December 7, 2018: Tissue Barriers
Kiminori Sato
1. The human vocal fold is a vibrating tissue and vascular structures in organs which have the capacity to vibrate require a specific structure suitable for vibration. 2. The structure of the blood vessels is unique at the vocal fold edge as a vibrating tissue, where only small vessels, including arterioles, venules, and capillaries, are present. The capillaries are distributed in the superficial layer of the lamina propria (Reinke's space). 3. The blood vessels enter the vocal fold edge from the anterior or posterior end of the membranous vocal fold and run essentially parallel to the vocal fold edge...
2018: Advances in Experimental Medicine and Biology
Lan Chen, Wen Li, Daoxin Wang
To explore the effects of honokiol (HKL) on pulmonary microvascular endothelial cells in lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) and the underlying mechanisms.
 Methods: In animal experiment, a total of 40 C57BL/6J mice were randomly divided into a control group (Con group), a LPS intervention group (LPS group), a LPS+honokiol (HKL) intervention group (HKL group) and a LPS+HKL+nicotinamide (NAM) intervention group (NAM group) (n=10 in each group). In the cell experiment, the experiment cells were divided into a control group (Con group), a LPS intervention group (LPS group), a LPS+HKL intervention group (HKL group), a LPS+HKL+NAM intervention group (NAM group), and a LPS+HKL+compound C (CMC) intervention group (CMC group)...
October 28, 2018: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
Hideharu Abe, Akiko Sakurai, Arisa Ochi
The glomerulus is a network of capillaries known as a tuft, located at the beginning of a nephron in the kidney. Here we describe a novel method for the induction of a macroscopically visible three-dimensional glomerulus-like sphere (GLS). This procedure did not require any additional cytokines and completed the formation of spheres within 24 h. After the formation was complete, GLS maintained a steady state for at least five days without proliferation and without a decrease in viability. Therefore, this procedure assists various assays for a prolong period of time...
December 3, 2018: Biochemical and Biophysical Research Communications
Jia Zhang, Yanyan Guo, Wanyu Ge, Xia Zhou, Minglin Pan
Mellithemia are diabetic patients' emblematic syndrome, which would induce vasculopathy resulting from apoptosis of vascular endothelial cells. The pathological mechanism of high glucose-induced apoptosis of vascular endothelial cells is investigated in the present study utilizing HUVEC cells. As high glucose-induced apoptosis is caused by elevated mitochondrial permeability-mediated release of mitochondrial cytochrome c, voltage-dependent anion channel (VDAC1), the controller of mitochondrial permeability, and its regulator Bax were investigated...
December 1, 2018: Die Pharmazie
Jeroen P Kooman, Frank M van der Sande
BACKGROUND: Abnormalities in fluid status in hemodialysis (HD) patients are highly prevalent and are related to adverse outcomes. SUMMARY: The inherent discontinuity of the HD procedure in combination with an often compromised cardiovascular response is a major contributor to this phenomenon. In addition, systemic inflammation and endothelial dysfunction are related to extracellular fluid overload (FO). Underlying this relation may be factors such as hypoalbuminemia and an increased capillary permeability, leading to an altered fluid distribution between the blood volume (BV) and the interstitial fluid compartments, compromising fluid removal during dialysis...
December 5, 2018: Blood Purification
Zhimeng Lv, Ming Guo, Chenghua Li, Yina Shao, Xuelin Zhao, Weiwei Zhang
Vascular endothelial growth factor (VEGF) is a key conservative regulator of inflammation response by promoting cell proliferation, migration, and vascular permeability. It also induces the release of inflammatory factors in vertebrates. We previously characterized NLR family pyrin domain containing 3 and HMGB3 homology in Apostichopus japonicus, providing the occurrence of inflammation in this species. However, to our knowledge, other inflammation-related molecules, such as VEGF, have rarely been investigated...
December 2, 2018: Developmental and Comparative Immunology
Rana Shafabakhsh, Esmat Aghadavod, Majid Ghayour-Mobarhan, Gordon Ferns, Zatollah Asemi
Retinopathy, characterized by an alteration of the retinal microvasculature, is a common complication of diabetes mellitus. These changes can cause increased permeability and alter endothelial cell proliferation, edema, and abnormal neovascularization and eventually result in blindness. The pathogenesis of diabetic retinopathy (DR) is complicated, involving many factors/mediators such as genetic susceptibility, microRNAs, and cytokines. One of the factors involved in DR pathogenesis is epigenetic changes that can have a key role in the regulation of gene expression; these include microRNAs, histone modifications, and methylation of DNA...
December 4, 2018: Journal of Cellular Physiology
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