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Endothelial loss

Tomáš Vaisar, Erica Couzens, Arnold Hwang, Michael Russell, Carolyn E Barlow, Laura F DeFina, Andrew N Hoofnagle, Francis Kim
AIMS/HYPOTHESIS: One of the hallmarks of diabetes is impaired endothelial function. Previous studies showed that HDL can exert protective effects on endothelium stimulating NO production and protecting from inflammation and suggested that HDL in obese people with diabetes and dyslipidemia may have lower endothelial protective function. We aimed to investigate whether type 2 diabetes impairs HDL endothelium protective functions in people with otherwise normal lipid profile. METHODS: In a case-control study (n = 41 per group) nested in the Cooper Center Longitudinal Study we tested the ability of HDL to protect endothelium by stimulating endothelial nitric oxide synthase activity and suppressing NFκB-mediated inflammatory response in endothelial cells...
2018: PloS One
Antoine Abou Jaoude, Lise Badiqué, Mohamed Mlih, Sara Awan, Sunning Guo, Alexandre Lemle, Clauda Abboud, Sophie Foppolo, Lionel Host, Jérôme Terrand, Hélène Justiniano, Joachim Herz, Rachel L Matz, Philippe Boucher
ShcA is an adaptor protein that binds to the cytoplasmic tail of receptor tyrosine kinases and of the Low Density Lipoprotein-related receptor 1 (LRP1), a trans-membrane receptor that protects against atherosclerosis. Here, we examined the role of endothelial ShcA in atherosclerotic lesion formation. We found that atherosclerosis progression was markedly attenuated in mice deleted for ShcA in endothelial cells, that macrophage content was reduced at the sites of lesions, and that adhesion molecules such as the intercellular adhesion molecule-1 (ICAM-1) were severely reduced...
March 14, 2018: Scientific Reports
Shigeru Kinoshita, Noriko Koizumi, Morio Ueno, Naoki Okumura, Kojiro Imai, Hiroshi Tanaka, Yuji Yamamoto, Takahiro Nakamura, Tsutomu Inatomi, John Bush, Munetoyo Toda, Michio Hagiya, Isao Yokota, Satoshi Teramukai, Chie Sotozono, Junji Hamuro
BACKGROUND: Corneal endothelial cell (CEC) disorders, such as Fuchs's endothelial corneal dystrophy, induce abnormal corneal hydration and result in corneal haziness and vision loss known as bullous keratopathy. We investigated whether injection of cultured human CECs supplemented with a rho-associated protein kinase (ROCK) inhibitor into the anterior chamber could increase CEC density. METHODS: We performed an uncontrolled, single-group study involving 11 persons who had received a diagnosis of bullous keratopathy and had no detectable CECs...
March 15, 2018: New England Journal of Medicine
Aaron Strumwasser, Aditi Bhargava, Gregory P Victorino
INTRODUCTION: Translocation of phosphatidylserine from the inner leaflet to the outer leaflet of the endothelial membrane via phospholipid scramblase-1 (PLSCR1) is an apoptotic signal responsible for the loss of endothelial barrier integrity after ischemia-reperfusion injury. We hypothesized that inhibiting phosphatidylserine expression on endothelial cells would attenuate ischemia-reperfusion (IRI) induced increases in hydraulic permeability (Lp). METHODS: Mesenteric hydraulic permeability (Lp) was measured in rat post-capillary mesenteric venules subjected to IRI via superior mesenteric artery (SMA) occlusion (45 minutes) and release (300 minutes) in conjunction with several inhibitors of phosphatidylserine exposure as follows: 1) inhibition of PLSCR1 translocation (DTE - dithioerythritol, n=3), 2) inhibition of PLSCR1 membrane trafficking (2-BP - 2-bromopalmitate, n=3), and 3) inhibition of ion exchange necessary for PLSCR1 function (DIDS - 4,4'-Diisothiocyano-2,2'-stilbenedisulfonic acid, n=3)...
March 12, 2018: Journal of Trauma and Acute Care Surgery
Eva Nüsken, Jörg Dötsch, Lutz T Weber, Kai-Dietrich Nüsken
Chronic kidney disease affects more than 10% of the population. Programming studies have examined the interrelationship between environmental factors in early life and differences in morbidity and mortality between individuals. A number of important principles has been identified, namely permanent structural modifications of organs and cells, long-lasting adjustments of endocrine regulatory circuits, as well as altered gene transcription. Risk factors include intrauterine deficiencies by disturbed placental function or maternal malnutrition, prematurity, intrauterine and postnatal stress, intrauterine and postnatal overnutrition, as well as dietary dysbalances in postnatal life...
2018: Frontiers in Pediatrics
Véronique Beaulieu Leclerc, Olivier Roy, Kim Santerre, Stéphanie Proulx
Human corneal endothelial cells (HCECs) easily become fibroblastic-like when cultured, rendering them unsuitable for tissue engineering of the cornea. Transforming growth factor β (TGF-β) could be a key factor in this phenomenon; however, TGF-β is also known to maintain the endothelium in a quiescent state in vivo. This work aimed to compare the effects of TGF-β1 on the phenotype of HCECs during the proliferation and maturation phases. Our results show that addition of TGF-β1 during the active proliferation phase produced fibroblastic HCECs and loss of the cell junction markers ZO-1 and n-cadherin, independent from the presence of epidermal growth factor (EGF)...
March 13, 2018: Scientific Reports
Leilei Mao, Tuo Yang, Xin Li, Xia Lei, Yang Sun, Yongfang Zhao, Wenting Zhang, Yanqin Gao, Baoliang Sun, Feng Zhang
The major pathophysiological process of vascular cognitive impairment (VCI) is chronic cerebral ischemia, which causes disintegration of the blood-brain barrier (BBB), neuronal death, and white matter injury. This study aims to test whether sulforaphane (Sfn), a natural activator of nuclear factor erythroid 2-related factor 2 (Nrf2), reduces the chronic ischemic injury and cognitive dysfunction after VCI. Experimental VCI was induced in rats by permanent occlusion of both common carotid arteries for six weeks...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
Katharina Wulf, Michael Teske, Claudia Matschegewski, Daniela Arbeiter, Dalibor Bajer, Thomas Eickner, Klaus-Peter Schmitz, Niels Grabow
The successive incorporation of several drugs into the polymeric bulk of implants mostly results in loss of considerable quantity of one drug, and/or the loss in quality of the coating and also in changes of drug release time points. A dual drug delivery system (DDDS) based on poly-L-lactide (PLLA) copolymers combining the effective inhibition of smooth muscle cell proliferation while simultaneously promoting re-endothelialization was successfully developed. To overcome possible antagonistic drug interactions and the limitation of the polymeric bulk material as release system for dual drugs, a novel concept which combines the bulk and surface drug immobilization for a DDDS was investigated...
March 12, 2018: Drug Delivery and Translational Research
Karen L Price, Maria Kolatsi-Joannou, Chiara Mari, David A Long, Paul J D Winyard
Kidney function is directly linked to the number of nephrons which are generated until 32-36 weeks gestation in humans. Failure to make nephrons during development leads to congenital renal malformations, whilst nephron loss in adulthood occurs in progressive renal disease. Therefore, an understanding of the molecular processes which underlie human nephron development may help design new treatments for renal disease. Mesenchyme to epithelial transition (MET) is critical for forming nephrons, and molecular pathways which control rodent MET have been identified...
December 2018: Cell Death Discovery
Juliana Vieira Dias, Celine Gloaguen, Dimitri Kereselidze, Line Manens, Karine Tack, Teni G Ebrahimian
A central question in radiation protection research is whether low-dose and low-dose-rate (LDR) exposures to ionizing radiation play a role in progression of cardiovascular disease. The response of endothelial cells to different LDR exposures may help estimate risk of cardiovascular disease by providing the biological mechanism involved. We investigated the effect of chronic LDR radiation on functional and molecular responses of human aorta endothelial cells (HAoECs). Human aorta endothelial cells were continuously irradiated at LDR (6 mGy/h) for 15 days and analyzed at time points when the cumulative dose reached 0...
January 2018: Dose-response: a Publication of International Hormesis Society
Antonella Cotoia, Lucia Mirabella, Sabrina Altamura, Rachele Villani, Flavia Marchese, Giuseppe Ferrara, Karim Mariano, Tullo Livio, Gilda Cinnella
BACKGROUND: Sepsis caused by complicated intra-abdominal infection is associated with high mortality. Loss of endothelial barrier integrity, inflammation, and impaired cellular oxygen have been shown to be primary contributors to sepsis. To date, little is known regarding the pathway for the mobilization of endothelial progenitor cells (EPCs) from the bone marrow in sepsis whereas stromal-cell-derived factor 1a (SDF-1a) and hypoxia inducible factor 1 (HIF-1) seem to have a role in the EPC response to hypoxic microenvironments...
March 12, 2018: Trials
Di Yang, ChenXi Xiao, Fen Long, ZhengHua Su, WanWan Jia, Ming Qin, MengWei Huang, WeiJun Wu, Rinkiko Suguro, XinHua Liu, YiZhun Zhu
Aims: Angiotensin II (Ang II) causes vascular inflammation, leading to vascular endothelial cell dysfunction, and is associated with the development of cardiovascular diseases. Therefore, interventions in inflammation may contribute to the reduction of cardiovascular diseases. Here, we aim to demonstrate that HDAC4, one of class IIa family histone deacetylases (HDACs) members, promotes autophagy-dependent vascular inflammation. Methods and results: By loss-of-function approaches, our study provides the first evidence that HDAC4 mediates Ang II-induced vascular inflammation in vitro and in vivo...
February 24, 2018: Cardiovascular Research
Hironosuke Watanabe, Hisashi Sahara, Shunichiro Nomura, Tatsu Tanabe, Dilrukshi K Ekanayake-Alper, Lennan K Boyd, Nathan J Louras, Arsenoi Asfour, Makenzie A Danton, Siu-Hong Ho, Scott J Arn, Robert J Hawley, Akira Shimizu, Takeshi Nagayasu, David Ayares, Marc I Lorber, Megan Sykes, David H Sachs, Kazuhiko Yamada
BACKGROUND: Despite recent progress in survival times of xenografts in non-human primates, there are no reports of survival beyond 5 days of histologically well-aerated porcine lung grafts in baboons. Here, we report our initial results of pig-to-baboon xeno-lung transplantation (XLTx). METHODS: Eleven baboons received genetically modified porcine left lungs from either GalT-KO alone (n = 3), GalT-KO/humanCD47(hCD47)/hCD55 (n = 3), GalT-KO/hD47/hCD46 (n = 4), or GalT-KO/hCD39/hCD46/hCD55/TBM/EPCR (n = 1) swine...
March 12, 2018: Xenotransplantation
Yongchang Lai, Zhijian Zhao, Tao Zeng, Xiongfa Liang, Dong Chen, Xiaolu Duan, Guohua Zeng, Wenqi Wu
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC), and is frequently accompanied by the genetic features of von Hippel-Lindau (VHL) loss. VHL loss increases the expression of hypoxia-inducible factors (HIFs) and their targets, including epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF). The primary treatment for metastatic RCC (mRCC) is molecular-targeted therapy, especially anti-angiogenic therapy...
2018: Cancer Cell International
Xin Zhao, Jinyu Liu, Shijun Yang, Dandan Song, Chen Wang, Chen Chen, Chengcheng Wang, Feifei Pu, Runmei Yang, Xiaoya Li, Qiuting Wang, Shasha Ge, Yulin Lin, Xiuhua Liu, Dayong Cai
Vascular dementia (VaD) is the common cognitive disorder derived mainly from lacunar stroke. The neurovascular coupling (NVC) dysfunction involves in its pathogenesis. VaD lacks suitable animal models for developing preventive therapies. This study aimed to confirm a model for preventing VaD via maintaing NVC sensitivity in rats. The model was replicated with autologous microthrombi against the background of hypercholesterolemia. A phosphodiesterase inhibitor (pentoxyfylline) was preventively administrated to confirm the role of NVC sensitivity...
March 8, 2018: European Journal of Pharmacology
Jonathan W Crews, Marianne O Price, Jeferson Lautert, Matthew T Feng, Francis W Price
PURPOSE: To identify whether intraoperative hyphema from the peripheral iridotomy during Descemet membrane endothelial keratoplasty (DMEK) is associated with anticoagulant or antiplatelet use, age, combined phacoemulsification, or adverse outcomes. SETTING: Price Vision Group, Indianapolis, Indiana, USA. DESIGN: Retrospective case series. METHODS: Data were obtained from consecutive DMEK cases with an intraoperative iridotomy from July 2015 through July 2016...
March 7, 2018: Journal of Cataract and Refractive Surgery
Tamer M Abdelghany, Raed S Ismail, Fatma A Mansoor, Joseph R Zweier, Frazer Lowe, Jay L Zweier
Cigarette smoking (CS) is a well-established risk factor for cardiovascular disease (CVD). Endothelial dysfunction (ED) with loss of nitric oxide (NO) production is a central mechanism leading to the advent of CVD. Despite many prior studies of this major health problem, the exact mechanism by which CS induces ED is not well understood. This study examines the mechanism by which CS induces ED with altered endothelial NO synthase (eNOS) function in aortic endothelial cells (AECs). Exposure of AECs to cigarette smoke extract (CSE) resulted in a marked decrease in NO production with concomitant increase in superoxide (O2 ...
March 7, 2018: Nitric Oxide: Biology and Chemistry
Paula M Calvo, Rosa R de la Cruz, Angel M Pastor
Vascular endothelial growth factor (VEGF), also known as VEGF-A, was discovered due to its vasculogenic and angiogenic activity, but a neuroprotective role for VEGF was later proven for lesions and disorders. In different models of motoneuronal degeneration, VEGF administration leads to a significant reduction of motoneuronal death. However, there is no information about the physiological state of spared motoneurons. We examined the trophic role of VEGF on axotomized motoneurons with recordings in alert animals using the oculomotor system as the experimental model, complemented with a synaptic study at the confocal microscopy level...
March 6, 2018: Experimental Neurology
Brant M Wagener, Parker J Hu, Joo-Yeun Oh, Cilina A Evans, Jillian R Richter, Jaideep Honavar, Angela P Brandon, Judy Creighton, Shannon W Stephens, Charity Morgan, Randal O Dull, Marisa B Marques, Jeffrey D Kerby, Jean-Francois Pittet, Rakesh P Patel
BACKGROUND: Trauma is the leading cause of death and disability in patients aged 1-46 y. Severely injured patients experience considerable blood loss and hemorrhagic shock requiring treatment with massive transfusion of red blood cells (RBCs). Preclinical and retrospective human studies in trauma patients have suggested that poorer therapeutic efficacy, increased severity of organ injury, and increased bacterial infection are associated with transfusion of large volumes of stored RBCs, although the mechanisms are not fully understood...
March 2018: PLoS Medicine
Nir Sorkin, Mahmood Showail, Adi Einan-Lifshitz, Tanguy Boutin, Armand Borovik, Mohammad Kreimei, Amir Rosenblatt, Clara C Chan, David S Rootman
PURPOSE: To analyze the outcomes of Descemet membrane endothelial keratoplasty (DMEK) in eyes with previous Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS: This retrospective interventional case series included 26 eyes (26 patients) that underwent DMEK to replace a previous DSAEK graft with at least 6 months of follow-up. The outcome measures were indications for surgery, best spectacle-corrected visual acuity (BSCVA), endothelial cell density, rebubbling rate, rejection, and failure...
March 6, 2018: Cornea
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