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Endothelial loss

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https://www.readbyqxmd.com/read/29331583/importins-%C3%AE-and-%C3%AE-signaling-mediates-endothelial-cell-inflammation-and-barrier-disruption
#1
Antony Leonard, Arshad Rahman, Fabeha Fazal
Nucleocytoplasmic shuttling via importins is central to the function of eukaryotic cells and an integral part of the processes that lead to many human diseases. In this study, we addressed the role of α and β importins in the mechanism of endothelial cell (EC) inflammation and permeability, important pathogenic features of many inflammatory diseases such as acute lung injury and atherosclerosis. RNAi-mediated knockdown of importin α4 or α3 each inhibited NF-κB activation, proinflammatory gene (ICAM-1, VCAM-1, and IL-6) expression, and thereby endothelial adhesivity towards HL-60 cells, upon thrombin challenge...
January 10, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29330478/interaction-of-suppressor-of-cytokine-signalling-3-with-cavin-1-links-socs3-function-and-cavin-1-stability
#2
Jamie J L Williams, Nasser Alotaiq, William Mullen, Richard Burchmore, Libin Liu, George S Baillie, Fred Schaper, Paul F Pilch, Timothy M Palmer
Effective suppression of JAK-STAT signalling by the inducible inhibitor "suppressor of cytokine signalling 3" (SOCS3) is essential for limiting signalling from cytokine receptors. Here we show that cavin-1, a component of caveolae, is a functionally significant SOCS3-interacting protein. Biochemical and confocal imaging demonstrate that SOCS3 localisation to the plasma membrane requires cavin-1. SOCS3 is also critical for cavin-1 stabilisation, such that deletion of SOCS3 reduces the expression of cavin-1 and caveolin-1 proteins, thereby reducing caveola abundance in endothelial cells...
January 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29330144/kindlin-1-promotes-pulmonary-breast-cancer-metastasis
#3
Sana Sarvi, Hitesh Patel, Jun Li, Georgia L Dodd, Helen Creedon, Morwenna Muir, Jocelyn Ward, John C Dawson, Martin Lee, Jayne Culley, Donald M Salter, Andrew H Sims, Adam Byron, Valerie G Brunton
In breast cancer, increased expression of the cytoskeletal adaptor protein Kindlin-1 has been linked to increased risks of lung metastasis, but the functional basis is unknown. Here we show that in a mouse model of polyomavirus middle T antigen-induced mammary tumorigenesis, loss of Kindlin-1 reduced early pulmonary arrest and later development of lung metastasis. This phenotype relied on the ability of Kindlin-1 to bind and activate β integrin heterodimers. Kindlin-1 loss reduced α4 integrin-mediated adhesion of mammary tumor cells to the adhesion molecule VCAM-1 on endothelial cells...
January 12, 2018: Cancer Research
https://www.readbyqxmd.com/read/29329541/a-role-for-endothelial-nitric-oxide-synthase-in-intestinal-stem-cell-proliferation-and-mesenchymal-colorectal-cancer
#4
Jon Peñarando, Laura M López-Sánchez, Rafael Mena, Silvia Guil-Luna, Francisco Conde, Vanessa Hernández, Marta Toledano, Victoria Gudiño, Michela Raponi, Caroline Billard, Carlos Villar, César Díaz, José Gómez-Barbadillo, Juan De la Haba-Rodríguez, Kevin Myant, Enrique Aranda, Antonio Rodríguez-Ariza
BACKGROUND: Nitric oxide (NO) has been highlighted as an important agent in cancer-related events. Although the inducible nitric oxide synthase (iNOS) isoform has received most attention, recent studies in the literature indicate that the endothelial isoenzyme (eNOS) can also modulate different tumor processes including resistance, angiogenesis, invasion, and metastasis. However, the role of eNOS in cancer stem cell (CSC) biology and mesenchymal tumors is unknown. RESULTS: Here, we show that eNOS was significantly upregulated in VilCre ERT2 Apc fl/+ and VilCre ERT2 Apc fl/fl mouse intestinal tissue, with intense immunostaining in hyperproliferative crypts...
January 10, 2018: BMC Biology
https://www.readbyqxmd.com/read/29329121/technique-for-preparing-ultrathin-and-nanothin-descemet-stripping-automated-endothelial-keratoplasty-tissue
#5
Albert Y Cheung, Joshua H Hou, Peter Bedard, Veronique Grimes, Natalie Buckman, Medi Eslani, Edward J Holland
PURPOSE: To describe and report outcomes of our single-pass microkeratome technique for preparation of ultrathin (UT, ≤100 μm) and nanothin (NT, ≤50 μm) Descemet stripping automated endothelial keratoplasty (DSAEK) grafts. METHODS: To prepare NT-DSAEK grafts, a pachymetry nomogram specific to each technician and individual microkeratome head was developed based on accumulated precut and postcut pachymetry data from previous DSAEK grafts. Mean graft thickness as well as precut and postcut endothelial cell counts (ECCs) of NT-DSAEK, UT-DSAEK, and Descemet membrane endothelial keratoplasty (DMEK) grafts between July 2015 and July 2017 were calculated and compared statistically...
January 11, 2018: Cornea
https://www.readbyqxmd.com/read/29328026/clinical-efficacy-of-s-adenosylmethionine-in-patients-with-non-alcoholic-steatohepatitis-and-chronic-kidney-disease-i-ii-stage
#6
A Antoniv, N Antofiychuk, T Danylyshina, I Trefanenko, V Shuper
The article presents a theoretical generalization of the results of the clinical efficacy of S-adenosylmethionine in patients with non-alcoholic steatohepatitis (NASH) in comorbidity with obesity and chronic kidney disease (CKD) of the 1st-2nd stages. The objective of the article was to determine the likely effect of S-adenosylmethionine and Meldonium on the clinical course of non-alcoholic steatohepatitis (NASH) and chronic kidney disease (CKD) of the I-II stages. We examined 75 patients with NASH with comorbid obesity I degree and CKD I and II dgrees...
December 2017: Georgian Medical News
https://www.readbyqxmd.com/read/29320761/expandable-arterial-endothelial-precursors-from-human-cd34-cells-differ-in-their-proclivity-to-undergo-an-endothelial-to-mesenchymal-transition
#7
Auston Z Miller, Alexander Satchie, Alex P Tannenbaum, Aman Nihal, James A Thomson, David T Vereide
Arterial diseases continue to pose a major health concern but in vitro studies are limited because explanted cells can exhibit poor proliferative capacity and a loss of specificity. Here, we find that two transcription factors, MYCN and SOX17, induce and indefinitely expand in culture precursors of human arterial endothelial cells (expandable arterial endothelial precursors [eAEPs]). The eAEPs are derived from CD34+ cells found in umbilical cord blood or adult bone marrow. Independent eAEP lines differ in their proclivity to undergo an endothelial-to-mesenchymal transition (EndoMT), a hallmark event in a broad array of vascular diseases and disorders...
January 9, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29318471/aav-mediated-gene-delivery-of-the-calreticulin-anti-angiogenic-domain-inhibits-ocular-neovascularization
#8
Leilei Tu, Jiang-Hui Wang, Veluchamy A Barathi, Selwyn M Prea, Zheng He, Jia Hui Lee, James Bender, Anna E King, Grant J Logan, Ian E Alexander, Youn-Shen Bee, Ming-Hong Tai, Gregory J Dusting, Bang V Bui, Jingxiang Zhong, Guei-Sheung Liu
Ocular neovascularization is a common pathological feature in diabetic retinopathy and neovascular age-related macular degeneration that can lead to severe vision loss. We evaluated the therapeutic efficacy of a novel endogenous inhibitor of angiogenesis, the calreticulin anti-angiogenic domain (CAD180), and its functional 112-residue fragment, CAD-like peptide 112 (CAD112), delivered using a self-complementary adeno-associated virus serotype 2 (scAAV2) in rodent models of oxygen-induced retinopathy and laser-induced choroidal neovascularization...
January 9, 2018: Angiogenesis
https://www.readbyqxmd.com/read/29317961/successful-treatment-of-rapidly-progressive-life-threatening-esophageal-submucosal-hematoma-in-a-patient-with-van-der-hoeve-syndrome
#9
Yasuhiro Watanabe, Naomi Shimizu, Masahiro Iwakawa, Takashi Yamaguchi, Noriko Ban, Hidetoshi Kawana, Atsuhito Saiki, Emiko Sakaida, Chiaki Nakaseko, Yasuhiro Matsuura, Nobuyuki Aotsuka, Hideaki Bujo, Ichiro Tatsuno
Osteogenesis imperfecta (OI) is a rare inherited disorder of the connective tissue with many reports on its association with bleeding diatheses. OI patients with blue sclera, hearing loss, and bone vulnerability are classified as having van der Hoeve syndrome. Here, we report the first case of rapidly progressing, massive esophageal submucosal hematoma in this syndrome. Bleeding in OI is reportedly due to defective capillary integrity and platelet dysfunction; however, our patient did not show such findings...
February 2018: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/29317302/bu-shen-tong-luo-decoction-prevents-bone-loss-via-inhibition-of-bone-resorption-and-enhancement-of-angiogenesis-in-ovariectomy-induced-osteoporosis-of-rats
#10
Han Yuan, Linyan Xiao, Wen Min, Wenchao Yuan, Shengfeng Lu, Guicheng Huang
ETHNOPHARMACOLOGICAL RELEVANCE: Gathering three ancient formulas, traditional Chinese medicine Bu-Shen-Tong-Luo decoction (BSTLD) has been used to treat postmenopausal osteoporosis (PMO) at the Jiangsu Province Hospital of Chinese Medicine for decades. However, the effect of BSTLD on angiogenesis and bone resorption as well as its possible mechanism are still unknown. AIM OF THE STUDY: This study was aimed to evaluate the preventive effect of BSTLD on ovariectomy-induced bone loss and vasculature disorder, and to investigate the possible bone protection mechanism of BSTLD in inhibiting bone resorption by enhancing angiogenesis signaling in ovariectomy-induced osteoporosis of rats...
January 6, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29314250/inhibition-of-camkk2-enhances-fracture-healing-by-stimulating-indian-hedgehog-signaling-and-accelerating-endochondral-ossification
#11
Justin N Williams, Anuradha Valiya Kambrath, Roshni B Patel, Kyung Shin Kang, Elsa Mével, Yong Li, Ying-Hua Cheng, Austin J Pucylowski, Mariah A Hassert, Michael J Voor, Melissa A Kacena, William R Thompson, Stuart J Warden, David B Burr, Matthew R Allen, Alexander G Robling, Uma Sankar
Approximately ten percent of all bone fractures do not heal, resulting in patient morbidity and healthcare costs. However, no pharmacological treatments are currently available to promote efficient bone healing. Inhibition of Ca2+ /calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) reverses age-associated loss of trabecular and cortical bone volume and strength in mice. In the current study, we investigated the role of CaMKK2 in bone fracture healing and show that its pharmacological inhibition using STO-609 accelerates early cellular and molecular events associated with endochondral ossification, resulting in a more rapid and efficient healing of the fracture...
January 3, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29306791/empagliflozin-rescues-diabetic-myocardial-microvascular-injury-via-ampk-mediated-inhibition-of-mitochondrial-fission
#12
Hao Zhou, Shuyi Wang, Pingjun Zhu, Shunying Hu, Yundai Chen, Jun Ren
Impaired cardiac microvascular function contributes to diabetic cardiovascular complications although effective therapy remains elusive. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor recently approved for treatment of type 2 diabetes, promotes glycosuria excretion and offers cardioprotective actions beyond its glucose-lowering effects. This study was designed to evaluate the effect of empagliflozin on cardiac microvascular injury in diabetes and the underlying mechanism involved with a focus on mitochondria...
December 30, 2017: Redox Biology
https://www.readbyqxmd.com/read/29304082/striated-muscle-gene-therapy-for-the-treatment-of-lipoprotein-lipase-deficiency
#13
Katherine E Gadek, Hong Wang, Monica N Hall, Mitchell Sungello, Andrew Libby, Drew MacLaskey, Robert H Eckel, Bradley B Olwin
Excessive circulating triglycerides due to reduction or loss of lipoprotein lipase activity contribute to hypertriglyceridemia and increased risk for pancreatitis. The only gene therapy treatment for lipoprotein lipase deficiency decreases pancreatitis but minimally reduces hypertriglyceridemia. Synthesized in multiple tissues including striated muscle and adipose tissue, lipoprotein lipase is trafficked to blood vessel endothelial cells where it is anchored at the plasma membrane and hydrolyzes triglycerides into free fatty acids...
2018: PloS One
https://www.readbyqxmd.com/read/29303887/correlation-between-postoperative-central-corneal-thickness-and-endothelial-damage-after-cataract-surgery-by-phacoemulsification
#14
Jean Marc Perone, Mathilde Boiche, Louis Lhuillier, Francis Ameloot, Shamour Premy, Anne-Laure Jeancolas, Christophe Goetz, Estelle Neiter
PURPOSE: To study the correlation between postoperative corneal edema and endothelial cell loss after cataract surgery by microcoaxial phacoemulsification. METHODS: Eighty-five eyes of 85 consecutive patients with mild cataract (up to C5, N4, and P5: per LOCS III classification) were included in a prospective study from September 2014 to November 2014. Eighty-five eyes were necessary to obtain a precision of 0.15 for computation of the Pearson correlation coefficient...
January 4, 2018: Cornea
https://www.readbyqxmd.com/read/29303444/reductions-in-brain-pericytes-are-associated-with-arteriovenous-malformation-vascular-instability
#15
Ethan A Winkler, Harjus Birk, Jan-Karl Burkhardt, Xiaolin Chen, John K Yue, Diana Guo, W Caleb Rutledge, George F Lasker, Carlene Partow, Tarik Tihan, Edward F Chang, Hua Su, Helen Kim, Brian P Walcott, Michael T Lawton
OBJECTIVE Brain arteriovenous malformations (bAVMs) are rupture-prone tangles of blood vessels with direct shunting of blood flow between arterial and venous circulations. The molecular and/or cellular mechanisms contributing to bAVM pathogenesis and/or destabilization in sporadic lesions have remained elusive. Initial insights into AVM formation have been gained through models of genetic AVM syndromes. And while many studies have focused on endothelial cells, the contributions of other vascular cell types have yet to be systematically studied...
January 5, 2018: Journal of Neurosurgery
https://www.readbyqxmd.com/read/29302788/wide-field-contact-specular-microscopy-analysis-of-corneal-endothelium-post-trabeculectomy
#16
Naoki Okumura, Daiki Matsumoto, Yugo Okazaki, Noriko Koizumi, Chie Sotozono, Shigeru Kinoshita, Kazuhiko Mori
PURPOSE: This study investigates the possible role of the filtration bleb in the continuous decrease in corneal endothelial cell (CEC) density observed following trabeculectomy. METHODS: This study involved 51 eyes of 37 glaucoma patients who underwent trabeculectomy. The CEC density was determined by contact specular microscopy in three areas: (1) the cornea center, (2) near the trabeculectomy filtration bleb, and (3) the opposite side of the bleb. The eyes were grouped according to post-surgical follow-up years: 0-1 (Group 1), 1-2 (Group 2), 2-3 (Group 3), 3-4, (Group 4), and 4+ years (Group 5)...
January 4, 2018: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/29301417/isolated-kidney-perfusion-the-influence-of-pulsatile-flow
#17
Charlotte von Horn, Thomas Minor
Within the scope of transplantation research, ex vivo kidney perfusion has been proven an attractive model to study ischemia-reperfusion and preservation injury. Renal perfusion techniques also occupy scientists with the aim to optimize organ reconditioning and preparation prior to transplantation. This study investigated the influence of a pulsatile perfusion pattern that brings flow conditions closer to physiological situations, on renal perfusion characteristic and kidney function in the isolated perfused kidney...
January 4, 2018: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/29299782/chronic-mild-hypoxia-promotes-profound-vascular-remodeling-in-spinal-cord-blood-vessels-preferentially-in-white-matter-via-an-%C3%AE-5%C3%AE-1-integrin-mediated-mechanism
#18
Sebok K Halder, Ravi Kant, Richard Milner
Spinal cord injury (SCI) leads to rapid destruction of neuronal tissue, resulting in devastating motor and sensory deficits. This is exacerbated by damage to spinal cord blood vessels and loss of vascular integrity. Thus, approaches that protect existing blood vessels or stimulate the growth of new blood vessels might present a novel approach to minimize loss or promote regeneration of spinal cord tissue following SCI. In light of the remarkable power of chronic mild hypoxia (CMH) to stimulate vascular remodeling in the brain, the goal of this study was to examine how CMH (8% O2 for up to 7 days) affects blood vessel remodeling in the spinal cord...
January 3, 2018: Angiogenesis
https://www.readbyqxmd.com/read/29298774/kidney-transplantation-in-a-patient-lacking-cytosolic-phospholipase-a2-proves-renal-origins-of-urinary-pgi-m-and-tx-m
#19
Jane Mitchell, Rebecca B Knowles, Nicholas S Kirkby, Daniel M Reed, Matthew L Edin, William E White, Melissa V Chan, Hilary Longhurst, Magdi Yaqoob, Ginger L Milne, Darryl C Zeldin, Timothy D Warner
Rationale: The balance between vascular prostacyclin which is anti-thrombotic and platelet thromboxane A2 which is pro-thrombotic is fundamental to cardiovascular health. Prostacyclin and thromboxane A2 are formed following the concerted actions of cytosolic phospholipase A2 (cPLA2α) and cyclooxygenase. Urinary 2,3-dinor-6-keto PGF1α (PGI-M) and 11-dehydro-TXB2 (TX-M) have been taken as biomarkers of prostacyclin and thromboxane A2 formation with the circulation and used to explain cyclooxygenase biology and patient phenotypes, despite concerns that urinary PGI-M and TX-M originate in the kidney...
January 3, 2018: Circulation Research
https://www.readbyqxmd.com/read/29296907/tlr2-agonism-reverses-chemotherapy-induced-neutropenia-in-macaca-fascicularis
#20
Nicholas J Laping, Michael P DeMartino, Joshua E Cottom, Jeffrey M Axten, John G Emery, Jeffrey H Guss, Miriam Burman, James J Foley, Mui Cheung, Allen Oliff, Sanjay Kumar
Neutropenia is a common consequence of radiation and chemotherapy in cancer patients. The resulting immunocompromised patients become highly susceptible to potentially life-threatening infections. Granulocyte colony-stimulating factor (G-CSF) is known to stimulate neutrophil production and is widely used as a treatment of chemotherapy-induced neutropenia. A small-molecule G-CSF secretagogue without a requirement for refrigerated supply chain would offer a more convenient and cost-effective treatment of chemotherapy-induced neutropenia...
December 12, 2017: Blood Advances
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