Endothelium (Total 217789 Papers Found)

PURPOSE BAY 43-9006 is a novel dual-action Raf kinase and vascular endothelial growth factor receptor inhibitor that inhibits tumor cell proliferation and angiogenesis. This study established the safety and pharmacokinetics of BAY 43-9006 in 69 patients with advanced refractory solid tumors. PATIENTS AND METHODS BAY 43-9006 (50 to 800 mg) was administered once or twice daily on a varying weekly schedule. Pharmacokinetic sampling was performed in all patients; preliminary tumor response was als ...
AIMS Increased dietary fish-oil consumption is associated with a reduced risk of coronary heart events and has pronounced effects on dyslipidaemia. However, the effects of fish-oil supplement on vascular function and metabolic profile in patients with Type 2 diabetes mellitus (DM) are unclear. METHODS In a double-blind placebo-controlled trial, we randomized 97 Type 2 DM patients without prior cardiovascular disease to fish-oil (4 g/day, n = 49) or olive-oil (with equivalent calories, as place ...
The chemokine stromal-derived factor-1 (SDF-1) and its unique receptor, CXCR4, are required for normal cardiovascular development, but a critical role for SDF-1 in postnatal vascular remodeling and the mechanisms underlying SDF-1/CXCR-4 vasculogenesis are unclear. Here we show that SDF-1 is expressed by the vascular endothelium from selected healthy and tumor tissues. In vitro, primary endothelial cells constitutively express SDF-1 that is detected in the cytoplasm, on the cell surface, and in t ...
Our study first proposed that curcumin could protect human endothelial cells from the damage caused by oxidative stress via autophagy. Furthermore, our results revealed that curcumin causes some novel cellular mechanisms that promote autophagy as a protective effect. Pretreatment with curcumin remarkably improves the survival of human umbilical vein endothelial cells (HUVECs) from H 2O 2-induced viability loss, which specifically evokes an autophagic response. Exposed to H 2O 2, curcumin-treated ...
Endothelial cells (ECs) express 2 members of the cadherin family, VE and N-cadherin. Although VE-cadherin induces EC homotypic adhesion, N-cadherin function in ECs remains largely unknown. EC-specific inactivation of either VE or N-cadherin leads to early fetal lethality suggesting that these cadherins play a nonredundant role in vascular development. We report here that VE-cadherin negatively controls junctional localization and expression of N-cadherin by limiting p120-catenin availability and ...
Brain endothelial cells are unique among endothelial cells in that they express apical junctional complexes, including tight junctions, which quite resemble epithelial tight junctions both structurally and functionally. They form the blood-brain-barrier (BBB) which strictly controls the exchanges between the blood and the brain compartments by limiting passive diffusion of blood-borne solutes while actively transporting nutrients to the brain. Accumulating experimental and clinical evidence indi ...
In contrast to the established role of blood vessel remodeling in inflammation, the biologic function of the lymphatic vasculature in acute inflammation has remained less explored. We studied 2 established models of acute cutaneous inflammation, namely, oxazolone-induced delayed-type hypersensitivity reactions and ultraviolet B irradiation, in keratin 14-vascular endothelial growth factor (VEGF)-C and keratin 14-VEGF-D transgenic mice. These mice have an expanded network of cutaneous lymphatic v ...
1. Endothelial cells are permanently challenged by altering pH in the blood, and oxidative damage could also influence the intracellular pH (pHi) of the endothelium. Cerebral microvascular endothelial cells form the blood–brain barrier (BBB) and pHi regulation of brain capillary endothelial cells is important for the maintenance of BBB integrity. The aim of this study was to address the pH regulatory mechanisms and the effect of an acute exposure to hydrogen peroxide (H2O2) on the pH regulatio ...
BACKGROUND Chronic alcohol consumption has been associated with enhanced susceptibility to both systemic and mucosal infections. However, the exact mechanisms underlying this enhanced susceptibility remain incompletely understood. METHODS Using a nonhuman primate model of ethanol (EtOH) self-administration, we examined the impact of chronic alcohol exposure on immune homeostasis, cytokine, and growth factor production in peripheral blood, lung, and intestinal mucosa following 12 months of chro ...
OBJECTIVE To examine matrix metalloproteinase 9 (MMP-9) in the synovial fluid (SF) and synovial membrane (SM) in relation to vascular endothelial cell (EC) apoptosis, vascular endothelial growth factor (VEGF), and SM vascular pattern. METHODS Thirty-four patients underwent needle arthroscopy of the knee joint; 12 had early rheumatoid arthritis (RA), 12 had early psoriatic arthritis (PsA), and 10 had osteoarthritis (OA). The early RA and early PsA patients were matched for disease activity. SF ...
A novel siRNA delivery system based on polyelectrolyte complex (PEC) micelles was introduced in this study. Vascular endothelial growth factor (VEGF) siRNA was conjugated to poly(ethylene glycol) (PEG) via a disulfide linkage (siRNA-PEG). The siRNA-PEG conjugate could form PEC micelles by interacting with cationic polyethylenimine (PEI) as a core forming agent. The VEGF siRNA-PEG/PEI PEC micelles showed greater stability than naked VEGF siRNA against enzymatic degradation. Under a reductive cond ...
We studied acute responses of rat lungs to inhalation of urban particulate matter and ozone. Exposure to particles (40 mg/m3 for 4 hours; mass median aerodynamic diameter, 4 to 5 microm; Ottawa urban dust, EHC-93), followed by 20 hours in clean air, did not result in acute lung injury. Nevertheless, inhalation of particles resulted in decreased production of nitric oxide (nitrite) and elevated secretion of macrophage inflammatory protein-2 from lung lavage cells. Inhalation of ozone (0.8 parts p ...
Biochemical and cell fractionation studies suggest caveolae contain functionally organized sets of signaling molecules that are capable of transmitting specific signals to the cell. It is not known, however, whether any signals actually originate from caveolae in living cells. To address this question, we have engineered the calcium sensor yellow cameleon so that it is targeted either to the plasma membrane, caveolae, or the cytoplasm of endothelial cells. Quantitative measurements of the three ...
A procedure for the isolation of osteopontin (OPN) from bovine milk using ion-exchange and hydrophobic chromatography is described. A DEAE-Sephacel column followed by dual phenyl-Sepharose columns yielded approximately 8 mg of purified protein per liter of milk. SDS-PAGE analysis revealed that the protein migrated at M(r) 60,000. NH2-terminal sequence analysis of the first seven amino acids revealed the protein to be identical to that previously reported for bovine OPN. Also, our preparation dem ...
Notch signaling is essential for embryonic vascular development in mammals and other vertebrates. Here we show that mouse embryos with conditional activation of the Notch1 gene in endothelial cells (Notch1 gain of function embryos) exhibit defects in vascular remodeling increased diameter of the dorsal aortae, and form arteriovenous malformations. Conversely, embryos with either constitutive or endothelial cell-specific Notch1 gene deletion also have vascular defects, but exhibit decreased diame ...
PURPOSE OF REVIEW This review will survey recent findings on the cholesterol transport and scavenger functions of scavenger receptor BI. Although scavenger receptor BI and CD36 bind many of the same ligands, these two receptors have very specific lipid transport functions: CD36 facilitates the uptake of long chain fatty acids and SR-BI mediates the transport of cholesterol and cholesteryl ester from HDL particles. Scavenger receptor BI is a physiologically relevant HDL receptor that, along with ...
The retinal vasculature provides a unique window to assess vascular health noninvasively and directly in vivo. Advances in fundus photography and retinal image analysis techniques have enabled the objective and accurate assessment of quantitative retinal vascular caliber measurement. Over the last decade, large population-based studies have shown that retinal vascular calibers are associated with a wide range of subclinical (e.g. atherosclerosis, inflammation and endothelial dysfunction) and cli ...
Plasminogen activator inhibitor type-1 (PAI-1) is a major physiological inhibitor of fibrinolysis, with its plasma levels correlating with the risk for myocardial infarction and venous thrombosis. The regulation of PAI-1 transcription by endothelial cells (ECs), a major source of PAI-1, remains incompletely understood. Adipocytes also produce PAI-1, suggesting possible common regulatory pathways between adipocytes and ECs. Peroxisomal proliferator-activated receptor-gamma (PPAR)gamma is a ligand ...
Recruitment of polymorphonuclear neutrophils (PMNs) remains a paramount prerequisite in innate immune defense and a critical cofounder in inflammatory vascular disease. Neutrophil recruitment comprises a cascade of concerted events allowing for capture, adhesion and extravasation of the leukocyte. Whereas PMN rolling, binding, and diapedesis are well characterized, receptor-mediated processes, mechanisms attenuating the electrostatic repulsion between the negatively charged glycocalyx of leukocy ...
Hepatic insulin resistance is an important underlying cause of the metabolic syndrome that manifests itself in diseases such as diabetes type II, atherosclerosis or non-alcoholic fatty liver disease (NAFLD). In this paper, we summarize comprehensively the current state of knowledge pertaining to the molecular mechanisms that lead to insulin resistance in hepatocytes and sinusoidal liver cells. In hepatocytes, the insulin resistant state is brought about by at least one, but more likely by a comb ...
Conditioned medium (secretome) derived from an enriched stem cell culture stimulates chemotaxis of human fibroblasts. These cells are classified as multipotent murine mesenchymal stromal cells (mMSC) by immunochemical analysis of marker proteins. Proteomic analysis of mMSC secretome identifies nineteen secreted proteins, including extracellular matrix structural proteins, collagen processing enzymes, pigment epithelium-derived factor (PEDF) and cystatin C. Immunodepletion and reconstitution expe ...
Bilateral femurs of 12-week-old female Sprague-Dawley rats were fractured, and the fractured femurs were harvested 36 h, 3, 7, 10, and 14 days after the fracture. Localization of cell proliferation in the fracture calluses was investigated using immunohistochemistry with antiproliferating cell nuclear antigen (PCNA) monoclonal antibodies. Thirty-six hours after the fracture, many PCNA-positive cells were observed in the whole callus. The change was not limited to mesenchymal cells at the fractur ...
Endothelial cell activation and dysfunction are involved in the pathophysiology of ARDS. Circulating endothelial cells (CECs) may be a useful marker of endothelial dysfunction and damage but have been poorly studied in ARDS. We hypothesized that the CEC count may be elevated in patients with sepsis-related ARDS compared to those with sepsis without ARDS. ARDS was defined according to the Berlin consensus definition. The study population included 17 patients with moderate or severe ARDS, 9 with m ...
In addition to low-density lipoproteins, plasma chylomicrons and very-low-density lipoproteins (VLDL) contribute to atherogenesis. When triglyceride-rich particles bind to arterial endothelium and to deendothelialized areas, locally present lipoprotein lipase initiates triglyceride hydrolysis and decreases the size of the adhering particles. Additional changes in composition are brought about by the exchange of lipids between chylomicron/VLDL remnants and the cholesteryl ester-rich low- and high ...
The endothelial lining of the vasculature forms the physical barrier between the blood and underlying tissues. Junctions between adjacent endothelial cells are dynamically modulated to sustain vascular homeostasis and to support the transendothelial migration of leukocytes during inflammation. A variety of factors initiate intracellular signaling pathways that regulate the opening and resealing of junctional complexes. This review focuses on three primary signaling pathways initiated within endo ...
BACKGROUND Cyclooxygenase (COX)-2 expression and tumour-induced angiogenesis appear to be increased in squamous cell carcinoma (SCC) of the skin. In other cancers, COX-2 is a pro-angiogenic factor. The association between angiogenesis and COX-2 has not been studied in skin cancer. OBJECTIVES To assess the onset of increased COX-2 expression and angiogenesis in the multistage carcinogenesis of SCC as well as the correlation between those two parameters. PATIENTS/METHODS We performed a retrosp ...
Semantic Scholar extracted view of "Vinculin associates with endothelial VEcadherin VEcadherin VEcadherin junctions to control forcedependent forcedependent forcedependent remodeling" by Stephan Huveneers et al. ...
BACKGROUND AND PURPOSE Pre-menopausal females have a lower incidence of cardiovascular disease compared with age-matched males, implying differences in the mechanisms and pathways regulating vasoactivity. In small arteries, myogenic tone (constriction in response to raised intraluminal pressure) is a major determinant of vascular resistance. Endothelium-derived dilators, particularly NO, tonically moderate myogenic tone and, because the endothelium is an important target for female sex hormones, ...
This study presents a multicellular computational model of a rat mesenteric arteriole to investigate the signal transduction mechanisms involved in the generation of conducted vasoreactivity. The model comprises detailed descriptions of endothelial (ECs) and smooth muscle (SM) cells (SMCs), coupled by nonselective gap junctions. With strong myoendothelial coupling, local agonist stimulation of the EC or SM layer causes local changes in membrane potential (V(m)) that are conducted electrotonicall ...
Solid tumors must induce new blood vessels if they are to grow beyond minimal size. As an initial step in this process, tumors secrete a vascular permeability factor that renders the local microvasculature hyperpermeable to fibrinogen and to other plasma proteins. Extravasated fibrinogen is rapidly clotted to crosslinked fibrin gel. Over time, this gel is invaded by macrophages, fibroblasts, and endothelial cells and undergoes "organization," such that it is replaced by vascularized granulation ...
IN spite of better understanding and considerable improvement in the management and early care of patients with spinal cord injury, venous thrombo-embolism still remains a major complication during the acute stage after admission. The high morbidity of this vascular pathology in paraplegics has been thoroughly investi­ gated by Walsh (1965), Watson (1968) and Dollfuss (1971), who reported an incidence of thrombo-embolic complications of 13 per cent in their units. Concepts regarding the mechani ...
The aim of the study was to evaluate VEGF expression in tumour biopsies as a prognostic factor for radiotherapy outcome in advanced carcinoma of the cervix. A retrospective study was carried out on 100 patients. Pre-treatment tumour VEGF expression was examined immunohistochemically in formalin-fixed, paraffin-embedded biopsies using a widely available commercial antibody. A semi-quantitative analysis was made using a scoring system of 0, 1, 2, and 3, for increasing intensity of staining. High V ...
A 38-kd protein that associates with F-actin structures in activated platelets and endothelial cells was purified, cloned, and characterized. The protein contains an N-terminal PDZ motif, a large intervening sequence, and a C-terminal LIM domain and was identified as the human homolog of rat CLP36. The study showed that CLP36 associates with actin filaments and stress fibers that are formed during shape change and spreading of platelets and during migration and contraction of endothelial cells. ...
Leukocytes extravasate from the blood in response to physiologic or pathologic demands by means of complementary ligand interactions between leukocytes and endothelial cells. The multistep model of leukocyte extravasation involves an initial transient interaction ("rolling" adhesion), followed by secondary (firm) adhesion. We recently showed that binding of CD44 on activated T lymphocytes to endothelial hyaluronan (HA) mediates a primary adhesive interaction under shear stress, permitting extrav ...
How mechanotransduction intersects with chemical and transcriptional factors to shape organogenesis is an important question in developmental biology. This is particularly relevant to the cardiovascular system, which uses mechanical signals from flowing blood to stimulate cytoskeletal and transcriptional responses that form a highly efficient vascular network. Using this system, artery size and structure are tightly regulated, but the underlying mechanisms are poorly understood. Here, we demonst ...
Vascular endothelial dysfunction (VED) is an important factor in the initiation and development of atherosclerosis (AS). Previous studies have demonstrated that endothelial permeability is increased in diet‑induced AS. However, the precise underlying mechanisms remain poorly understood. The present study aimed to analyze whether the myosin light chain kinase (MLCK) inhibitor ML7 is able to improve VED and AS by regulating the expression of the tight junction (TJ) proteins zona occludens (ZO) ...
A canine model with cyclic flow variations (CFVs) in stenosed and endothelium-injured coronary arteries was used to examine the role of active oxygen species in platelet aggregation in vivo. We studied 90 anesthetized dogs in which the pericardial cavity was opened and the heart was exposed. The velocity of blood flow in the left anterior descending coronary artery (LAD) was monitored by a pulsed Doppler flow probe. In 67 dogs, the LADs were stenosed by applying external constrictors at the site ...
There is a major unmet medical need for effective and well-tolerated treatment options for patients with advanced nonsmall cell lung cancer (NSCLC), in both first-line and relapsed/refractory settings. Experimental evidence has validated signalling pathways that regulate tumour angiogenesis, including the vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) pathways, as valid anti-cancer drug targets. However, to date, bevacizumab (a ...
1. The effects of the inhibitor of nitric oxide synthase, N omega-nitro-L-arginine methylester (L-NAME, 10(-4) M), mechanical disruption of the endothelium and hypoxia on contraction to noradrenaline (alpha 1- and alpha 2-adrenoceptor agonist), phenylephrine (alpha 1-adrenoceptor agonist) and UK 14304 (alpha 2-adrenoceptor agonist) were compared in the rabbit isolated pulmonary artery. The effects of the selective antagonists rauwolscine (10(-6) M, alpha 2-adrenoceptors) and prazosin (10(-7) M, ...
Training has been shown to induce cardioprotection. The mechanisms involved remain still poorly understood. Aims of the study were to examine the relevance of training intensity on myocardial protection against ischemia/reperfusion (I/R) injury, and to which extent the beneficial effects persist after training cessation in rats. Sprague-Dawley rats trained at either low (60% $$ {\dot{{V}}\text{O}}_{2\max } $$ ) or high (80% $$ {\dot{{V}}\text{O}}_{2\max } $$ ) intensity for 10 weeks. An additio ...
Lectin-like oxidized low-density lipoprotein (Ox-LDL) receptor-1 (LOX-1) is a novel cell-surface receptor for Ox-LDL, which can be expressed by vascular endothelial cells, smooth muscle cells, and macrophages. On the other hand, transforming growth factor (TGF)-beta(1), which plays crucial roles in vascular remodeling and the pathogenesis of atherosclerosis, has been shown to inhibit expression of class A scavenger receptors and CD36 in macrophages. Here we provide the evidence that TGF-beta(1) ...
BACKGROUND Galectin-1 (gal-1), a member of the mammalian beta-galactoside-binding proteins, binds to cell surface glycoproteins (Mucin-1) on trophoblast cells. Although it has been demonstrated that gal-1 induces cell differentiation processes in these cells, no information on its signal transduction processes is available so far. As tyrosine phosphorylation is a major mechanism that controls multiple biological processes including cell differentiation, survival and proliferation, the aim of thi ...
Immunological studies of human endothelial cells have been performed almost entirely on endothelial cells (EC) derived from foetal (umbilical vein) or adult (aorta) large vessels. Immunologically these EC have in common the fact that they are negative for major histocompatibility complex (MHC) class II antigens (HLA-DR), in contrast to microvascular cells within the heart which are constitutively positive for HLA-DR antigens. Here we describe a simple method for isolating microvascular EC from c ...
The microvessels in the buttock skin of 15 patients with long-standing juvenile diabetes were studied both by electron microscopy and three-dimensional (3D) computer reconstruction of a prototypical diabetic postcapillary venule. Endothelial cell gaps were found in postcapillary venules and capillaries, but only in association with an increased deposition of basement membrane-like material in the vascular wall. In parallel with the increased amounts of deposited basement membrane-like material, ...
Cyclooxygenase (COX)-1- and COX-2-derived prostaglandins are implicated in the development and progression of several malignancies. We have recently demonstrated that treatment of ovarian carcinoma cells with endothelin-1 (ET-1) induces expression of both COX-1 and COX-2, which contributes to vascular endothelial growth factor (VEGF) production. In this study, we show that in HEY and OVCA 433 ovarian carcinoma cells, ET-1, through the binding with ETA receptor (ETAR), induces prostaglandin E2 (P ...
Type I plasminogen activator inhibitor (PAI-1) is a 50 kDa glycoprotein belonging to the serine protease superfamily. PAI-1 is consistently and dramatically upregulated in a variety of fibrotic diseases. The aim of this study was to compare PAI-1 expression in normal human buccal mucosa and oral submucous fibrosis (OSF) specimens and further explore the potential mechanism that may lead to induced PAI-1 expression. Twenty-five OSF specimens and six normal buccal mucosa were examined by immunohis ...
The present study has examined relationship between cutaneous microvessel injury and adhesion molecule expression on the endothelium by cytokines in NZBxNZWF1 (B/WF1) mice, a model for human systemic lupus erythematosus. In advanced ages associated with overt clinical manifestation, but not in early ages, neutrophils with a minor proportion of monocytes and lymphocytes mainly adhered to the endothelium of capillary and the venule with fragmentation (leukocytoclasis), leading to the vascular inju ...
A serum-free medium formulation - TUD-1 - was developed supporting growth of HUVEC in tissue culture. Special features of the basal medium formulation are highly elevated levels of glutamine and serine as well as the inclusion of N-acetylcysteine and phosphoascorbic acid. The cellular mitogenic needs are satisfied by bFGF, VEGF, EGF and liver growth factor. Further hormone supplementation consists of insulin and hydrocortisone. A protocoll for serum-free passage of HUVEC was established for seru ...