Search results for "Endothelial Cell"
showing 10 items of 497 documents
Dynamic in vivo Imaging of Microvasculature and Perfusion by Miniaturized Confocal Laser Microscopy
2008
<i>Introduction:</i> Microvasculature and associated pathologies mandate dynamic imaging. We evaluated a novel miniaturized confocal laser scanning probe for in vivo visualization of blood vessels, blood flow, cell tracking and perfusion in both healthy rodents and disease models.<i> Methods:</i> The hand-held confocal microscopy system allowed a 500- to 2,400-fold magnification at a dynamically variable imaging depth. Different intravital stains were used alone or in combination for tissue, nuclear, plasma and vascular endothelial cell staining and for blood flow visualization, and targeted staining for individual cell populations. <i>Results:</i> Precis…
Preconditioning by Mitochondrial Reactive Oxygen Species Improves the Proangiogenic Potential of Adipose-Derived Cells-Based Therapy
2009
Objective— Transplantation of adipose-derived stroma cells (ADSCs) stimulates neovascularization after experimental ischemic injury. ADSC proangiogenic potential is likely mediated by their ability to differentiate into endothelial cells and produce a wide array of angiogenic and antiapoptotic factors. Mitochondrial reactive oxygen species (ROS) have been shown to control ADSC differentiation. We therefore hypothesized that mitochondrial ROS production may change the ADSC proangiogenic properties. Methods and Results— The use of pharmacological strategies (mitochondrial inhibitors, antimycin, and rotenone, with or without antioxidants) allowed us to specifically and precisely modulate mito…
Δ5-Cholenoyl-amino acids as selective and orally available antagonists of the Epheephrin system
2015
The Eph receptor-ephrin system is an emerging target for the development of novel anti-angiogenic therapies. Research programs aimed at developing small-molecule antagonists of the Eph receptors are still in their initial stage as available compounds suffer from pharmacological drawbacks, limiting their application in vitro and in vivo. In the present work, we report the design, synthesis and evaluation of structure-activity relationships of a class of Δ(5)-cholenoyl-amino acid conjugates as Eph-ephrin antagonists. As a major achievement of our exploration, we identified N-(3β-hydroxy-Δ(5)-cholen-24-oyl)-L-tryptophan (UniPR1331) as the first small molecule antagonist of the Eph-ephrin syste…
A novel class of potent nonglycosidic and nonpeptidic pan-selectin inhibitors.
2006
An early step of the inflammatory response, the rolling of leukocytes on activated endothelial cells, is mediated by selectin/carbohydrate interactions. The tetrasaccharide sialy Lewisx is a ligand for E-, P-, and L-selectin and therefore serves as a lead structure for the development of analogues. A combination of synthesis and structure-based design allowed rapid optimization. The current lead 2a was evaluated in our E-selectin cell flow chamber assay where it proved to inhibit rolling and adhesion with an IC50 of 28+/-7 microM. The assays used are predictive for the in vivo efficacy of test compounds as shown for 2a in a proteose peptone induced peritonitis model of acute inflammation in…
Volatile Anesthetics Influence Blood-Brain Barrier Integrity by Modulation of Tight Junction Protein Expression in Traumatic Brain Injury
2012
Disruption of the blood-brain barrier (BBB) results in cerebral edema formation, which is a major cause for high mortality after traumatic brain injury (TBI). As anesthetic care is mandatory in patients suffering from severe TBI it may be important to elucidate the effect of different anesthetics on cerebral edema formation. Tight junction proteins (TJ) such as zonula occludens-1 (ZO-1) and claudin-5 (cl5) play a central role for BBB stability. First, the influence of the volatile anesthetics sevoflurane and isoflurane on in-vitro BBB integrity was investigated by quantification of the electrical resistance (TEER) in murine brain endothelial monolayers and neurovascular co-cultures of the B…
Liver Sinusoidal Endothelial Cells Are a Site of Murine Cytomegalovirus Latency and Reactivation▿
2009
ABSTRACT Latent cytomegalovirus (CMV) is frequently transmitted by organ transplantation, and its reactivation under conditions of immunosuppressive prophylaxis against graft rejection by host-versus-graft disease bears a risk of graft failure due to viral pathogenesis. CMV is the most common cause of infection following liver transplantation. Although hematopoietic cells of the myeloid lineage are a recognized source of latent CMV, the cellular sites of latency in the liver are not comprehensively typed. Here we have used the BALB/c mouse model of murine CMV infection to identify latently infected hepatic cell types. We performed sex-mismatched bone marrow transplantation with male donors …
Antiatherosclerotic Effects of Small-Molecular-Weight Compounds Enhancing Endothelial Nitric-Oxide Synthase (eNOS) Expression and Preventing eNOS Unc…
2008
Many cardiovascular diseases are associated with reduced levels of bioactive nitric oxide (NO) and an uncoupling of oxygen reduction from NO synthesis in endothelial NO synthase (eNOS uncoupling). In human endothelial EA.hy 926 cells, two small-molecular-weight compounds with related structures, 4-fluoro-N-indan-2-yl-benzamide (CAS no. 291756-32-6; empirical formula C16H14FNO; AVE9488) and 2,2-difluoro-benzo[1,3]dioxole-5-carboxylic acid indan-2-ylamide (CAS no. 450348-85-3; empirical formula C17H13F2NO3; AVE3085), enhanced eNOS promoter activity in a concentration-dependent manner; with the responsible cis-element localized within the proximal 263 base pairs of the promoter region. RNA int…
Redox Regulation of Dihydrofolate Reductase: Friend or Troublemaker?
2015
Oxidative stress is a hallmark of cardiovascular diseases1 and a major contributor to vascular dysfunction.2 On the basis on recent concepts, vascular oxidative stress is caused mainly by infiltrating inflammatory cells such as monocytes/macrophages or leucocytes,3,4 producing so-called kindling radicals that lead to the activation of secondary, vascular enzymatic sources of reactive oxygen species (mainly superoxide).2,5 A prominent example is the uncoupled nitric oxide (NO) synthase, which means that an NO-producing antiatherosclerotic enzyme is getting switched to a superoxide-producing proatherosclerotic enzyme.2 Molecular mechanisms causing endothelial NO synthase (eNOS) uncoupling or …
Nitroglycerin-induced endothelial dysfunction and tolerance involve adverse phosphorylation and S-glutathionylation of endothelial nitric oxide synth…
2011
Continuous administration of nitroglycerin (GTN) causes tolerance and endothelial dysfunction by inducing reactive oxygen species (ROS) production from various enzymatic sources, such as mitochondria, NADPH oxidase, and an uncoupled endothelial nitric oxide synthase (eNOS). In the present study, we tested the effects of type 1 angiotensin (AT(1))-receptor blockade with telmisartan on GTN-induced endothelial dysfunction in particular on eNOS phosphorylation and S-glutathionylation sites and the eNOS cofactor synthesizing enzyme GTP-cyclohydrolase I.Wistar rats were treated with telmisartan (2.7 or 8 mg/kg per day PO for 10 days) and with GTN (50 mg/kg per day SC for 3 days). Aortic eNOS phos…
Arterial and Venous Endothelia Display Differential Functional Fractalkine (CX 3 CL1) Expression by Angiotensin-II
2012
Objective— Angiotensin-II (Ang-II) promotes the interaction of mononuclear cells with arterioles and neutrophils with postcapillary venules. To investigate the mechanisms underlying this dissimilar response, the involvement of fractalkine (CX 3 CL1) was explored. Methods and Results— Enhanced CX 3 CL1 expression was detected in both cremasteric arterioles and postcapillary venules 24 hours after Ang-II intrascrotal injection. Arteriolar leukocyte adhesion was the unique parameter significantly reduced (83%) in animals lacking CX 3 CL1 receptor (CX 3 CR1). Human umbilical arterial and venous endothelial cell stimulation with 1 μmol/L Ang-II increased CX 3 CL1 expression, yet neutralization …