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endothelial permeability

Meng-Lu Zhu, Xiao-Ling Xu, Xiao-Juan Wang, Nan-Nan Zhang, Kong-Jun Lu, Jing Qi, Fei-Yang Jin, Di Liu, Yong-Zhong Du
Targeted Drug Delivery Systems (TDDS) have attracted wide attention with reduced drug side effects and improved anti-tumor efficacy in comparison with traditional preparations. While targeting moiety in existing TDDS principally focused on recognition of receptors on the surface of tumor cells, accumulation into tumor tissue only could be performed by enhanced permeability and retention effect and active transportation into tumor cells. Doxorubicin (DOX)-loaded sialic acid-dextran (Dex)-octadecanoic acid (OA) micelles (SA-Dex-OA/DOX) were designed for targeting hepatocellular carcinoma effectively...
August 15, 2018: Molecular Pharmaceutics
G S M Sundaram, Kristen Binz, Vedica Sharma, Melany Yeung, Vijay Sharma
Thioflavin T (ThT), a positively charged heterocyclic small molecule, is a widely used fluorescent marker of amyloid pathophysiology to confirm the cause of death in post mortem brain tissue of Alzheimer's disease (AD) patients. Literature precedents indicate that current positron emission tomography (PET) agents, such as 11 C-PIB and 18 F-flutemetamol, share significant structural similarity with ThT, a lipophilic dye which does not traverse the blood-brain barrier (BBB) to enable the detection of Aβ plaques in vivo ...
June 1, 2018: MedChemComm
Zheng Chai, Xintao Zhang, Kelly Michelle Rigsbee, Mei Wang, R Jude Samulski, Chengwen Li
Adeno-associated virus (AAV) vectors have been successfully used for transgene delivery in clinical trials. A systemic administration of AAV vectors has been proposed in order to achieve global transduction, which requires that the AAV vector is capable of crossing the blood vessels. It has been demonstrated that serum proteins are able to directly interact with AAV virions to enhance liver transduction. In this study, we investigate whether the serum proteins have the potential to increase the capacity of AAV to diffuse through the endothelial cells and deliver the transgene into the whole body...
August 11, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Jie Zhang, Jiaqi Huang, Tongyun Qi, Yizhou Huang, Yuting Lu, Tianwei Zhan, Hui Gong, Zhengyi Zhu, Yueli Shi, Jianhong Zhou, Luyang Yu, Xue Zhang, Hongqiang Cheng, Yuehai Ke
Vascular endothelial (VE)-cadherin junctional localization is known to play a central role in vascular development, endothelial barrier integrity, and homeostasis. The sarcoma (Src) homology (SH) domain containing protein tyrosine phosphatase (SHP)2 has been shown to be involved in regulating endothelial barrier function; however, the mechanisms remain largely unknown. In this work SHP2 knockdown in an HUVEC monolayer increased VE-cadherin internalization and endothelial barrier permeability. Loss of SHP2 specifically augmented the GTPase activity of ADP-ribosylation factor (ARF)-1...
August 13, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Wenjun Wang, Emmanuel M Lollis, François Bordeleau, Cynthia A Reinhart-King
Tumor vasculature is known to be more permeable than the vasculature found in healthy tissue, which in turn can lead to a more aggressive tumor phenotype and impair drug delivery into tumors. While the stiffening of the stroma surrounding solid tumors has been reported to increase vascular permeability, the mechanism of this process remains unclear. Here, we utilize an in vitro model of tumor stiffening, ex ovo culture, and a mouse model to investigate the molecular mechanism by which matrix stiffening alters endothelial barrier function...
August 13, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Gui-Li Yang, Lu-Yuan Li
Vascular hyperpermeability occurs in angiogenesis and several pathobiological conditions, producing elevated interstitial fluid pressure and lymphangiogenesis. How these closely related events are modulated is a fundamentally important question regarding the maintenance of vascular homeostasis and treatment of disease conditions such as cancer, stroke, and myocardial infarction. Signals mediated by vascular endothelial growth factor receptors, noticeably VEGFR-1, -2, and -3, are centrally involved in the promotion of both blood vessel and lymphatic vessel growth...
2018: Signal Transduction and Targeted Therapy
Jang-Hyuk Yun, Young Jun Koh, Han-Seok Jeong, Da-Hye Lee, Eun Hui Lee, Chung-Hyun Cho
Retinopathy of prematurity (ROP) is an eye disease that causes blindness due to delayed vascular growth, retinal ischemia, and resulting abnormal angiogenesis. Nonselective β-antagonist propranolol is in clinical trials for the treatment of ROP due to its effect of reducing VEGF expression and inhibiting retinal angiogenesis in oxygen-induced ROP models (OIR), but the mechanism by which propranolol acts on ROP vessels is still unclear. In the present study, we have focused on the effect of propranolol on pericyte survival and vascular permeability...
August 9, 2018: Biochemical and Biophysical Research Communications
Yanjun Guo, Xin Yang, Jialin He, Jingjing Liu, Shiming Yang, Hui Dong
Ca2+ -sensing receptor (CaSR), a member of G protein-coupled receptor family, is widely expressed in the vascular system, including perivascular neurons, vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs). When stimulated, CaSR can further increase the cytosolic Ca2+ concentration ([Ca2+ ]cyt ) in two ways: intracellular Ca2+ release from endo/sarcoplasmic reticulum (ER/SR) and extracellular Ca2+ entry through Ca2+ -permeable cation channels. In endothelium, increased Ca2+ subsequently activate nitric oxide synthase (NOS) and intermediate conductance Ca2+ -activated K+ channels (IKCa), resulting in vasodilation through NOS-mediated NO release or membrane hyperpolarization...
August 8, 2018: Life Sciences
Chunwei Cheng, Jun Tan, Wei Qian, Lei Zhang, Xiaohua Hou
AIMS: Gut inflammation has been put forward to be associated with hepatic injury in the clinical practice. The dismantled intestinal barrier was highly concerned, however, largely unknown about the role of gut-vascular barrier (GVB) in this process. This study aimed to investigate if inflamed gut directly contributes to the progression of non-alcoholic steatohepatitis (NASH), especially attention to the GVB dysfunction. MAIN METHODS: Male C57bl/6 mice were fed with a high-fat diet (HFD) and 1% DSS for 12 weeks...
August 7, 2018: Life Sciences
Mohammed Nuru, Nino Muradashvili, Anuradha Kalani, David Lominadze, Neetu Tyagi
Methionine is an essential amino acid found in rich quantities in average American diet such as meats, fish and eggs. Excessive consumption of such food often exceeds the normal requirement of the methionine in our body; which found to be related to the development of neurodegenerative disorders. However, the mechanistic pathways of methionine's influence on the brain are unclear. The present study is focus on the effects of high methionine, low folate and low vitamin B6/B12 (HM-LF-LV) diet on the dysfunction of neuronal and vascular specific markers in the brain...
August 9, 2018: Metabolic Brain Disease
Vivian K Lee, Brett M Hosking, Joanna Holeniewska, Ewa C Kubala, Peter Lundh von Leithner, Peter J Gardner, Richard H Foxton, David T Shima
AIMS/HYPOTHESIS: Diabetic retinopathy is increasing in prevalence worldwide and is fast becoming a global epidemic and a leading cause of visual loss. Current therapies are limited, and the development of effective treatments for diabetic retinopathy requires a greater in-depth knowledge of disease progression and suitable modelling of diabetic retinopathy in animals. The aim of this study was to assess the early pathological changes in retinal morphology and neuronal, inflammatory and vascular features consistent with diabetic retinopathy in the ob/ob mouse model of type 2 diabetes, to investigate whether features similar to those in human diabetic retinopathy were present...
August 9, 2018: Diabetologia
Feng Zhang, Georgia Zarkada, Jinah Han, Jinyu Li, Alexandre Dubrac, Roxana Ola, Gael Genet, Kevin Boyé, Pauline Michon, Steffen E Künzel, Joao Paulo Camporez, Abhishek K Singh, Guo-Hua Fong, Michael Simons, Patrick Tso, Carlos Fernández-Hernando, Gerald I Shulman, William C Sessa, Anne Eichmann
Excess dietary lipid uptake causes obesity, a major global health problem. Enterocyte-absorbed lipids are packaged into chylomicrons, which enter the bloodstream through intestinal lymphatic vessels called lacteals. Here, we show that preventing lacteal chylomicron uptake by inducible endothelial genetic deletion of Neuropilin1 ( Nrp1 ) and Vascular endothelial growth factor receptor 1 ( Vegfr1 ; also known as Flt1 ) renders mice resistant to diet-induced obesity. Absence of NRP1 and FLT1 receptors increased VEGF-A bioavailability and signaling through VEGFR2, inducing lacteal junction zippering and chylomicron malabsorption...
August 10, 2018: Science
Jordi Pedragosa, Angélica Salas-Perdomo, Mattia Gallizioli, Roger Cugota, Francesc Miró-Mur, Ferran Briansó, Carles Justicia, Fernando Pérez-Asensio, Leonardo Marquez-Kisinousky, Xabier Urra, Anna Gieryng, Bozena Kaminska, Angel Chamorro, Anna M Planas
The central nervous system (CNS) contains several types of immune cells located in specific anatomic compartments. Macrophages reside at the CNS borders surrounding the brain vessels, in leptomeningeal spaces and the choroid plexus, where they interact with the vasculature and play immunological surveillance and scavenging functions. We investigated the phenotypic changes and role of these macrophages in response to acute ischemic stroke. Given that CD163 expression is a hallmark of perivascular and meningeal macrophages in the rat and human brain, we isolated CD163+ brain macrophages by fluorescence activated cell sorting...
August 9, 2018: Acta Neuropathologica Communications
Sena Iwata, Takahiko Imai, Masamitsu Shimazawa, Takashi Ishibashi, Masahiro Hayashi, Hideaki Hara, Shinsuke Nakamura
Astaxanthin is beneficial for human health and is used as a dietary supplement. The present study was performed in order to examine the protective effects of the astaxanthin derivative, adonixanthin, against cell death caused by hemoglobin, collagenase, lipopolysaccharide, and hydrogen peroxide, which are associated with hemorrhagic brain injury. In an in vitro study, adonixanthin exerted cytoprotective effects against each type of damage, and its effects were stronger than those of astaxanthin. The increased production of reactive oxygen species in human brain endothelial cells in the hemoglobin treatment group was inhibited by adonixanthin...
August 6, 2018: Brain Research
Nirmal S Sharma, Charitharth Vivek Lal, Jin-Dong Li, Xiang-Yang Lou, Liliana Viera, Tarek Abdallah, Robert King, Jaskaran Sethi, Prashanth Kanagarajah, Ricardo Restrepo-Jaramillo, Amanda Sales-Conniff, Shi Wei, Patricia L Jackson, J Edwin Blalock, Amit Gaggar, Xin Xu
ARDS is characterized by unrelenting PMN inflammation and vascular permeability. The matrikine proline-glycine-proline (PGP) and acetylated PGP (Ac-PGP) have been shown to induce PMN inflammation and endothelial permeability in vitro and in vivo. In this study, we investigated the presence and role of airway PGP peptides in acute lung injury (ALI)/ARDS. P. aeruginosa-derived LPS was instilled intratracheally (i.t) in mice to induce ALI and increased Ac-PGP with neutrophil inflammation was noted. The PGP inhibitory peptide, RTR (arginine-threonine-arginine), was administered (i...
August 9, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Guanghua Zhang, Xue Zhang, Haidi Huang, Yunxia Ji, Defang Li, Wanglin Jiang
Glucocorticoid insensitivity is an important barrier to the treatment of several inflammatory diseases, including acute lung injury (ALI). Saquinavir (SQV) is an inhibitor of the human immunodeficiency virus protease, and the therapeutic effects of SQV in ALI accompanied with glucocorticoid insensitivity have not been previously investigated. In this study, the effects of SQV on lipopolysaccharide (LPS)-mediated injury in human pulmonary microvascular endothelial cells (HPMECs), human type I alveolar epithelial cells (AT I), and alveolar macrophages were determined...
August 6, 2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Byeong Gon Kim, Pureun Haneul Lee, Sun Hye Lee, Ae Rin Baek, Jong Sook Park, Junehyuk Lee, Sung Woo Park, Do Jin Kim, Choon Sik Park, An Soo Jang
PURPOSE: The tight junction protein claudin-5 (CLDN5) is critical to the control of endothelial cellular polarity and pericellular permeability. The role of CLDN5 in chronic obstructive pulmonary disease (COPD) remains unclear. The aim of this study was to investigate the association between CLDN5 levels and clinical variables in patients with COPD. METHODS: In total, 30 patients with COPD and 30 healthy controls were enrolled in the study. The plasma CLDN5 level was checked in patients with stable or exacerbated COPD and in healthy controls...
September 2018: Allergy, Asthma & Immunology Research
Lichun Zhang, Qiuhe Li, Zhenning Liu, Wei Liu, Min Zhao
Fasudil, a rock kinase inhibitor, can inhibit systemic inflammation and prevent paraquat (PQ)-induced acute lung injuries in rats; however, the mechanisms for these protective effects remain elusive. This study investigated how the Rho/ROCK signaling pathway enables fasudil to protect against acute lung injuries in PQ-treated rats. Wistar rats (n = 240) were pretreated with fasudil (10 and 30 mg/kg, i.p.) 1 h prior to PQ administration. When compared to rats with PQ-induced lung injuries, rats pretreated with fasudil had significantly fewer polymorphonuclear neutrophils and lower concentrations of protein, TNF-α, IL-1β, and IL-6 in their bronchoalveolar lavage fluid...
August 7, 2018: Inflammation
Geetha B Heggannavar, Chinmay G Hiremath, Divya D Achari, Vishwas G Pangarkar, Mahadevappa Y Kariduraganavar
Brain glioma is the most lethal type of cancer, with extremely poor prognosis and high relapse. Unfortunately, the treatment of brain glioma is often limited because of the low permeability of anticancer drugs across the blood-brain barrier (BBB). To circumvent this, magnetic mesoporous nanoparticles were synthesized and loaded with doxorubicin as an anticancer agent. These nanoparticles were fabricated with Pluronic F-127 and subsequently conjugated with transferrin (Tf) to achieve the sustained release of the drug at the targeted site...
July 31, 2018: ACS Omega
Huan Qian, Zhangqi Dou, Wu Ruan, Pingyou He, John H Zhang, Feng Yan
Studies have suggested that blood-brain barrier (BBB) disruption contributes to the pathogenesis of early brain injury after subarachnoid haemorrhage (SAH). Activation of the receptor tyrosine kinase ErbB4 can cause intramembrane proteolysis and release a soluble intracellular domain (ICD) that modulates transcription in the nucleus. This study was carried out to investigate the potential roles of ErbB4 in preserving BBB integrity after experimental SAH, as well as the underlying mechanisms of its protective effects...
2018: Frontiers in Neuroscience
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