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Results for “Endothelialization”

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At least 307 records · Page 17Linked to original sources

PubMed1992

Production of neutrophil-specific lipid chemoattractant activity by cultured endothelial cells: heterogeneity dependent on species, ligand, or endothelial cell site of origin.

Previous studies have demonstrated that the interaction of cultured bovine aortic and pulmonary arterial endothelial cells and the proinflammatory vasoactive amines histamine, serotonin, and angiotensin II, causes production of three novel lipid neutrophil-specific chemoattractants that are distinct from other phospholipid or lipid neutrophil chemoattractants. In this study, we investigated the species and site specificity of this inflammatory response by incubating human aortic and pulmonary arterial endothelial cells with histamine, serotonin, and angiotensin II and assaying the supernatants for their effect on neutrophil migration. Each of these vasoactive amines caused production of neutrophil chemoattractant activity in a concentration dependent manner in both cell types. For each amine, production was blocked by a specific antagonist: cimetidine for histamine, methiothepin for serotonin-stimulated aortas, ketanserin for serotonin-stimulated pulmonary arteries, and saralasin for angiotensin II. In each case, all chemoattractant activity partitioned into the organic phase and resolution by HPLC yielded two chemotactic lipids. As with the lipid chemoattractants produced by bovine endothelial cells, these lipids did not coelute with PAF, LTB4, 5-HETE, or 15-HETE, nor did they increase lymphocyte or monocyte migration. The pattern of chemotactic activity following resolution by HPLC was similar in both human aortic and pulmonary arterial endothelial cells, but was different from that of bovine aortic and pulmonary arterial endothelial cells in that only two chemoattractant lipids appeared; the third chemotactic lipid was never produced. These studies demonstrate that human endothelial cells may actively participate in neutrophil enriched local inflammatory responses by production of neutrophil-specific chemotactic factors. They also suggest this response may be dissimilar depending on the site and species from which the endothelial cells originate.

Animals↗

PubMed1994

Basic fibroblast growth factor suppresses tissue plasminogen activator release from cultured human umbilical vein endothelial cells but enhances that from cultured human aortic endothelial cells.

Since basic fibroblast growth factor (bFGF) modulates the functions of vascular endothelial cells, we hypothesized that this factor may be involved in the regulation of the blood coagulation-fibrinolytic system mediated by the cells. Confluent cultures of vascular endothelial cells from human umbilical vein were treated with recombinant human bFGF (bFGF) in a serum-free medium and the content of tissue plasminogen activator antigen (t-PA:Ag) in the medium was determined by EIA. Treatment with bFGF resulted in a significant decrease in the release of t-PA:Ag from the cells accompanied with a less t-PA activity in the medium. In contrast, the t-PA:Ag release from human aortic endothelial cells was significantly increased by bFGF. The bFGF-induced decrease in the t-PA:Ag release from the venous endothelial cells was completely blocked by anti-bFGF antibody. The incorporation of [3H]leucine into the acid-insoluble fraction of the cells was significantly increased by bFGF; however, the activity of lactate dehydrogenase leaked into the medium was significantly decreased, suggesting that the suppression of the t-PA:Ag release caused by bFGF in the venous endothelial cells was not due to either a nonspecific inhibition of protein synthesis or a nonspecific cell damage. Since bFGF is postulated to be released from damaged endothelial cells, the present data suggest the regulation by bFGF of hemostasis mediated by endothelial cells when the vascular endothelium was damaged.

Aorta↗

PubMed2003

Modulation of endothelial Ca(2+)-activated K(+) channels by oxidized LDL and its contribution to endothelial proliferation.

OBJECTIVE: Oxidized low-density lipoprotein (oxLDL) plays an important role in causing endothelial dysfunction and initiating atherosclerosis. Some of the endothelial functions have been shown to be modulated by changes in cellular electrophysiological properties. Therefore, we analysed the effect of oxLDL on endothelial Ca(2+)-activated K(+) channels (BK(Ca)) and its contribution to oxLDL-mediated changes of proliferation and syntheses of nitric oxide (NO). METHODS: The patch-clamp technique was used to study the behavior of BK(Ca) in human endothelial cells of umbilical cord veins (HUVEC). Changes of intracellular Ca(2+) were measured by means of Fura-2 imaging. Cell counts and [3H]-thymidine incorporation were used to analyse endothelial proliferation. Synthesis of NO was measured by means of [3H]-cGMP radioimmunoassay. RESULTS: oxLDL (10 microg/ml) caused a significant increase of BK(Ca) activity, whereas preincubation of HUVEC with an antibody against the lectin-like-oxLDL-receptor-1 (LOX-1) abolished BK(Ca) activation. Fura-2 measurements revealed a biphasic increase of intracellular Ca(2+) after application of the atherogenic lipid. Endothelial proliferation was significantly increased by oxLDL. The highly selective BK(Ca) inhibitor iberiotoxin (100 nmol/l IBX) blocked this proliferative response. Acetylcholine-induced NO synthesis was significantly decreased by IBX. Interestingly, oxLDL significantly decreased acetylcholine-induced NO synthesis if the production of superoxide was not blocked by antisense oligonucleotides against the NAD(P)H-oxidase. CONCLUSIONS: Our data demonstrate that oxLDL activates BK(Ca), which plays an important role in oxLDL-mediated endothelial proliferation. Acetylcholine-induced NO synthesis is modulated by BK(Ca), whereas the reduction of acetylcholine-induced NO-synthesis by oxLDL is related to an increase in superoxide production.

Acetylcholine↗

PubMed2005

Inter-relationships of indices of endothelial damage/dysfunction [circulating endothelial cells, von Willebrand factor and flow-mediated dilatation] to tissue factor and interleukin-6 in acute coronary syndromes.

BACKGROUND: Increased circulating endothelial cells (CECs, reflecting endothelial damage) in acute coronary syndromes (ACS) has been reported. However, the inter-relationships of indices of endothelial damage/injury with development of vascular (dys)function, plasma levels of tissue factor (TF, an index of coagulation) and interleukin-6 (IL-6, a pro-inflammatory cytokine) have not been investigated in ACS. We hypothesized that increased CECs can be related to impaired flow-mediated vasodilatation (FMD, an index of endothelial dysfunction) and elevated plasma von Willebrand factor (vWf, also marking endothelial damage/dysfunction), TF and IL-6 in patients with ACS. METHODS: We studied 120 patients with ACS (80 acute myocardial infarction and 40 unstable angina; 86 male, age 65+/-12 years) and 40 matched patients with stable CAD and 40 healthy controls (HC) in a cross-sectional analysis. Plasma vWf, TF and IL-6 levels were measured by ELISA. CECs were quantified using epifluorescence microscope after immunomagnetic separation with CD146. Brachial artery FMD was assessed in a subset of 39 ACS patients. RESULTS: ACS patients had significantly higher CECs, vWf, TF and IL-6 levels, but lower FMD, when compared to stable CAD and HC (all p<0.001) and all were inter-correlated significantly. In ACS, CECs was strongly correlated with FMD (r=-0.64, p<0.001) and TF (r=0.7, p<0.001). In stable CAD, significant correlations were again found between many indices, but on multivariate analysis, IL-6 and vWf were both independently related to FMD. CONCLUSIONS: Increased CECs in ACS patients are closely associated with endothelial damage/dysfunction (vWf and FMD), coagulation (TF) and inflammation (IL-6). These inter-relationships support the concept of a central role of endothelial damage/injury in the activation of vascular and coagulation abnormalities in ACS.

Aged↗

PubMedDate not supplied

Effects of histamine 2 receptor antagonists on endothelial-neutrophil adhesion and surface expression of endothelial adhesion molecules induced by high glucose levels.

Neutrophil-endothelial adhesion is a crucial step in vascular inflammation and is recognized as a direct cause of serious atherosclerosis-mediated diseases. We previously demonstrated that high concentrations of glucose increased adhesion in a protein kinase C (PKC)-dependent manner within 48 h of administration by increasing the surface expression of endothelial adhesion molecules. In this study, we focused on the effects of histamine 2 receptor antagonists on endothelial-neutrophil adhesion and on the surface expression of endothelial adhesion molecules mediated by high glucose levels. Histamine 2 receptor antagonists have pleiotropic effects; they not only block the secretion of gastric acid, but also inhibit cell-cell adhesion, resulting in inhibition of metastasis. However, relevant mechanisms of action are not yet fully understood. Of three histamine 2 receptor antagonists (cimetidine, ranitidine, and famotidine), only cimetidine significantly attenuated adhesion mediated by 48-h incubation with 27.8 mM glucose. Cimetidine was found to decrease the surface expression of endothelial adhesion molecules intercellular adhesion molecule-1 and P-selectin, but not E-selectin. To determine the effects of cimetidine on intracellular level, we examined the effects of cimetidine on PKC-induced changes in adhesion, as well as the effects of nitric oxide (NO) synthase inhibitors on cimetidine. We found that NO synthase inhibitors reduced the inhibitory effects of cimetidine, whereas cimetidine did not affect adhesion mediated by a PKC activator. These data suggest that cimetidine acts directly on endothelial cells to inhibit high-glucose-induced expression of adhesion molecules and neutrophil adhesion mediated by increasing endothelial NO production, but not by inhibiting PKC.

Cell Adhesion↗

PubMed1996

Evidence of endothelial activation and endothelial activators in cord blood of infants of preeclamptic women.

OBJECTIVE: In preeclampsia markers of endothelial activation (e.g., increased cellular fibronectin and activities that alter in vitro endothelial function (e.g., stimulation of nitric oxide and prostacyclin generation) are increased in the maternal circulation. We tested preeclamptic infant blood for these markers and activities and correlated these findings with fetal growth. STUDY DESIGN: Plasma was obtained from 17 term nulliparcus preeclamptic and normal pregnant women and their infants and from 8 additional preeclamptic mother-baby pairs from earlier gestations. Plasma cellular fibronectin and production of nitric oxide and prostacyclin by cultured endothelial cells exposed to 2% plasma were measured. RESULTS: Cellular fibronectin was higher in maternal plasma of preeclamptic than nonpregnant women (6.1 +/- 0.29 vs 4.2 +/- 0.27 microgram/ml, p < 0.01), as were stimulated endothelial nitric oxide and prostacyclin production (nitric oxide 42.5 +/- 3.9 vs 26.9 +/- 2.3 nmol nitrite/microgram protein/24 hours, p < 0.05; prostacyclin 261.7 +/- 31.2 vs 151.9 +/- 18.7 pg prostaglandin F1 alpha/microgram protein/24 hours, p < 0.05). In the preeclamptic infants cellular fibronectin was also greater (3.3 +/- 0.15 vs 2.6 +/- 0.14 microgram/ml, p < 0.01), as was endothelial nitric oxide production in response to the plasma (24.4 +/- 1.1 vs 21.4 +/- 0.09 mumol/L nmol nitrite/microgram protein/24 hours, p < 0.05). Prostacyclin production was not significantly different. In preeclamptic infants across a wide gestational age there was no correlation of endothelial activation and fetal growth. CONCLUSIONS: Infants of women with preeclampsia may be affected by endothelial dysfunction, as well as reduced uteroplacental perfusion.

Adult↗

PubMed1999

Serum nitrite sensitively reflects endothelial NO formation in human forearm vasculature: evidence for biochemical assessment of the endothelial L-arginine-NO pathway.

OBJECTIVE: A reduced bioactivity of endothelial nitric oxide (NO) has been implicated in the pathogenesis of atherosclerosis. In humans, the endothelial L-arginine-NO pathway has been indirectly assessed via the flow response to endothelium-dependent vasodilators locally administered into the coronary, pulmonary or forearm circulation. However, biochemical quantification of endothelial NO formation in these organ circulations has been hampered so far because of the rapid metabolism of NO. Therefore, we aimed to work out a reliable biochemical index to assess endothelial NO formation in human circulation. METHODS: In 33 healthy volunteers, forearm blood flow (FBF) was measured by standard techniques of venous occlusion plethysmography at rest, after local application of the endothelium-dependent vasodilator acetylcholine (ACH), the endothelium-independent vasodilator papaverine (PAP), the stereospecific inhibitor of endothelial NO synthase (eNOS) L-NMMA, and L-arginine (ARG), the natural substrate of eNOS. In parallel, nitrite and nitrate concentrations in blood samples taken from the antecubital vein were measured by HPLC using anion-exchange chromatography in combination with electrochemical and ultraviolet detection following a specific sample preparation method. RESULTS: ACH dose-dependently increased resting FBF (from 3.0 +/- 0.3 to 10.4 +/- 0.9 ml/min per 100 ml tissue) and serum nitrite concentration (from 402 +/- 59 to 977 +/- 82 nmol/l, both p < 0.05, n = 12). A significant correlation was observed between the changes in FBF and the serum nitrite concentration (r = 0.61, p < 0.0001). L-NMMA reduced resting FBF and endothelium-dependent vasodilation by 30% and this was paralleled by a significant reduction in serum nitrite concentration at the highest dose of ACH (n = 9, p < 0.001). PAP increased FBF more than fourfold, but did not affect serum nitrite concentration (n = 11), whereas ARG significantly increased both FBF and nitrite. Basal serum nitrate amounted to 25 +/- 4 mumol/l and remained constant during the application of ACH, PAP and L-NMMA. CONCLUSIONS: The concentration of serum nitrite sensitively reflects changes in endothelial NO formation in human forearm circulation. This biochemical measure may help to characterize the L-arginine-NO pathway in disease states associated with endothelial dysfunction and to further elucidate its pathophysiological significance for the development of atherosclerosis in humans.

Acetylcholine↗

PubMed1982

Decreased endothelial permeability in the iridocorneal endothelial syndrome.

Five patients with the iridocorneal endothelial (ICE) syndrome were examined by fluorophotometry. All patients had typical abnormal corneal endothelium, peripheral anterior synechiae, and distortion of the iris (pupillary irregularity or anterior stromal traction tears) in one eye only. Fluorescein was deposited in the superior cornea of both eyes by iontophoresis, and the cornea and anterior chamber concentrations and total mass of fluorescein were measured hourly over the ensuing eight hours. In all five patients, the endothelial permeability to fluorescein was within normal limits in the normal eye. In four of the five abnormal eyes, endothelial permeability was markedly decreased. In these four patients, the permeability to fluorescein in the normal eye was approximately six times that in the abnormal eye. In the fifth patient, the endothelial permeability was normal in both eyes. The central corneal thicknesses were normal in both eyes of all five patients. These results indicate that in many eyes with the ICE syndrome, corneal endothelial permeability to solutes is markedly decreased. Decreased endothelial permeability to solutes has not been documented previously in any clinical corneal disorder and may be of importance in the pathophysiologic changes that accompany endothelial disease.

Adult↗

PubMedDate not supplied

Activation of endothelial cells by plasma from women with preeclampsia: differential effects on four endothelial cell types.

OBJECTIVE: To compare the ability of plasma from a population of women with preeclampsia and a population of plasma from women with normal pregnancies to activate four different endothelial cell types. METHODS: The secretion of nitrite and 6-keto prostaglandin F1 alpha by four endothelial cell types (isolated from the microvasculature of human decidua and skin, as well as a human umbilical vein endothelial cell line and a bovine coronary microvascular cell line) was assessed following a 24-hour incubation with plasma samples from the two groups. RESULTS: Nitrite production (an indicator of nitric oxide release) was detectable in only the decidual endothelial cells and the bovine microvascular endothelial cells (B-88), whereas 6-keto prostaglandin F1 alpha (stable metabolite of prostacyclin) was detectable in all cells. Only in the B-88 cells was there a greater production of nitrite or 6-keto prostaglandin F1 alpha in response to incubation with plasma from the preeclamptic patients when compared to plasma from the normotensive controls. CONCLUSION: The different responses of various endothelial cell types to the activating effects of plasma from preeclamptic women indicate that another important caveat to be considered when bioassaying for the circulating factor(s) of preeclampsia is the choice of endothelial cell to be studied.

Animals↗

PubMed2000

Scanning electron microscopic analysis of endothelial cell coverage and quality in large vessels from multi-organ donors: effects of preservation on endothelial cell integrity.

Endothelial cell integrity (coverage and quality) of large donor vessels is important because these vessels are used for vascular reconstructions in solid-organ transplantation. Disruption of the endothelial cell monolayer will initiate blood coagulation and may lead to thrombosis of large vessels, often resulting in the loss of the transplanted organ. Iliac arteries and veins, removed from 10 heart-beating multi-organ donors at the end of the donor procedure, were analyzed using scanning electron microscopy at three different time points of preservation. Endothelial cell coverage and quality were determined immediately after removal from the donor, after 10 h (time of transplantation) and 7 d storage in 'University of Wisconsin' cold preservation solution (UW). Endothelial cell coverage decreased during the preservation of arteries, but was maintained in veins. Storage of the veins for 7 d in plastic bags showed a decreased endothelial cell coverage compared to storage in glass vials. Early removal of the blood vessels and proper storage, free floating and in clean UW, may improve maintenance of the endothelial cell integrity. These findings may be important in order to reduce the risk of thrombosis and, consequently, organ failure after transplantation. Furthermore, vessels with maintained endothelial cell integrity after 7 d may be used for in vitro research.

Adenosine↗

PubMed2001

Endothelial nitric oxide synthase and caveolin-1 are co-localized in sinusoidal endothelial fenestrae.

BACKGROUND/AIMS: Nitric oxide is synthesized in diverse mammalian tissues by a family of calmodulin-dependent nitric oxide synthases (NOS). Caveolin, the principal structural protein in caveolae, interacts with endothelial NOS leading to enzyme inhibition in a reversible process modulated by Ca++-calmodulin. The aim of the present study was to clarify the ultrastructural localization of eNOS and caveolin-1 in hepatic sinusoidal endothelium by an electron immunogold method. METHODS: Male Wistar rats were used. Liver tissues and hepatic sinusoidal endothelial cells isolated from rat livers by collagenase infusion were studied. For immunohistochemistry, liver specimens were reacted with anti-eNOS or anti-caveolin-1 antibody. The ultrastructural localization of eNOS or caveolin-1 was identified by electron microscopy using an immunogold post-embedding method. RESULTS: Immunohistochemical studies using liver tissues localized endothelial NOS in hepatic sinusoidal lining cells, portal veins and hepatic arteries; and caveolin-1 in sinusoidal lining cells, bile canaliculi, portal vein and hepatic arteries. Immunogold particles indicating the presence of eNOS and caveolin-1 were demonstrated on the plasma membrane of sinusoidal endothelial fenestrae in liver tissue and also in isolated sinusoidal endothelial cells. CONCLUSION: Endothelial NOS and caveolin are co-localized on sinusoidal endothelial fenestrae, suggesting that interaction of the two may modulate cellular regulation of NO synthesis.

Animals↗

PubMed1995

Agonists for endothelial P2 purinoceptors trigger a signalling pathway producing Ca2+ responses in lymphocytes adherent to endothelial cells.

Recirculation of lymphocytes through the body involves their frequent adhesion to endothelial cells but little is known of the signalling pathways between these two cell types. Lymphocytes from patients with chronic lymphocytic leukaemia were loaded with the Ca(2+)-sensitive indicator, fura 2, and allowed to adhere to either glass or monolayers of human umbilical-vein endothelial cells. Addition of ATP or UTP (1-10 microM) to the superfusate produced a transient rise in cytosolic Ca2+ concentration in the lymphocytes adherent to endothelium (24 of 35 cells). In contrast, ATP or UTP (1-10 microM) had no effect on the cytosolic Ca2+ of lymphocytes attached to glass. As the only lymphocyte receptor for ATP (P2Z class) requires higher ATP concentrations ( > 50 microM) for Ca2+ influx and is unresponsive to UTP, the involvement of a lymphocyte P2Z purinoceptor is unlikely. Various agonists including ATP, UTP, 2-methylthioATP, ADP and histamine all stimulated increases in endothelial cytosolic Ca2+ but only ATP and UTP (both agonists for endothelial P2U purinoceptors) triggered Ca2+ transients in adherent lymphocytes. Removal of extracellular Ca2+ did not abolish the ATP-induced rise in cytosolic Ca2+ concentration in lymphocytes adherent to endothelial cells. These findings show that stimulation of endothelial P2U purinoceptors triggers an endothelial-lymphocyte signalling pathway which releases internal Ca2+ in adherent lymphocytes.

Adenosine Triphosphate↗

PubMed2002

Mast cells induce upregulation of P-selectin and intercellular adhesion molecule 1 on carotid endothelial cells in a new in vitro model of mast cell to endothelial cell communication.

It is suggested that mast cells contribute to cell recruitment in inflammation through the upregulation of endothelial adhesion molecules. P-selectin and intercellular adhesion molecule(ICAM)-1 are two key adhesion molecules that have been associated indirectly with mast cell activity. The canine C2 mastocytoma cell line and primary cultures of canine carotid endothelial cells were used to establish a new in vitro model to help study the interaction between mast cells and endothelial cells. Carotid endothelial cells were incubated with mast cell mediators to uncover their effect on endothelial ICAM-1 and P-selectin expression. To assess the relative contributions of tumour necrosis factor (TNF)-alpha and histamine to such effect, an H1 antihistamine and a TNF-alpha blocking antibody were used. Prior to activation by mast cell mediators, P-selectin was expressed only within the cytoplasm, and ICAM-1 was constitutively expressed on the surface of the canine carotid endothelial cells. Both adhesion molecules were enhanced significantly and strongly upon mast cell activation at various time points. Unstored TNF-alpha was fully responsible for ICAM-1 upregulation. P-selectin was up-regulated by both preformed and newly synthesized mast cell mediators, but neither histamine nor TNF-alpha accounted for such an effect. Therefore,a new model is proposed in which the pro-inflammatory effect of mast cells on endothelial cells can be studied in vitro. In this model, it has been demonstrated that only TNF-alpha accounts for the overexpression of ICAM-1 induced by mast cells, and that mast cells up-regulate P-selectin expression through a histamine-independent mechanism.

Animals↗

PubMed2002

Microbubble-endothelial cell interactions as a basis for assessing endothelial function.

Clinical signs and symptoms of coronary artery disease are predated in decades by endothelial dysfunction, an aberration in the vascular lining that permits the development and propagation of atherosclerotic lesions and vasomotor dysfunction in the arterial circulation. These ultimately lead to acute and chronic coronary ischemic syndromes. Other pathophysiologic scenarios encountered in clinical cardiology practice, such as cardiac transplant rejection and the period following coronary angioplasty or cardiac surgery, also are associated with endothelial dysfunction. Endothelial dysfunction parallels coronary risk factors and is potentially reversible, rendering early identification of the phenomenon a clinically important endpoint. Current methods for detecting endothelial dysfunction are limited, however. Myocardial contrast echocardiography using microbubbles targeted to bind to cell surface markers uniquely expressed by dysfunctional endothelial cells may offer an approach to the noninvasive detection of endothelial disease using clinical ultrasound imaging techniques. This article will discuss the concept of targeted ultrasound imaging and present preliminary studies in this area as applied to endothelial assessment. Potential applications to other disease states, both diagnostic and therapeutic, also are discussed.

Contrast Media↗

PubMed2005

Endothelial dihydrofolate reductase: critical for nitric oxide bioavailability and role in angiotensin II uncoupling of endothelial nitric oxide synthase.

Recent studies demonstrate that oxidative inactivation of tetrahydrobiopterin (H4B) may cause uncoupling of endothelial nitric oxide synthase (eNOS) to produce superoxide (O2*-). H4B was found recyclable from its oxidized form by dihydrofolate reductase (DHFR) in several cell types. Functionality of the endothelial DHFR, however, remains completely unknown. Here we present findings that specific inhibition of endothelial DHFR by RNA interference markedly reduced endothelial H4B and nitric oxide (NO.) bioavailability. Furthermore, angiotensin II (100 nmol/liter for 24 h) caused a H4B deficiency that was mediated by H2O2-dependent down-regulation of DHFR. This response was associated with a significant increase in endothelial O2*- production, which was abolished by eNOS inhibitor N-nitro-L-arginine-methyl ester or H2O2 scavenger polyethylene glycol-conjugated catalase, strongly suggesting H2O2-dependent eNOS uncoupling. Rapid and transient activation of endothelial NAD(P)H oxidases was responsible for the initial burst production of O2* (Rac1 inhibitor NSC 23766 but not an N-nitro-L-arginine-methyl ester-attenuated ESR O2*- signal at 30 min) in response to angiotensin II, preceding a second peak in O2*- production at 24 h that predominantly depended on uncoupled eNOS. Overexpression of DHFR restored NO. production and diminished eNOS production of O2*- in angiotensin II-stimulated cells. In conclusion, these data represent evidence that DHFR is critical for H4B and NO. bioavailability in the endothelium. Endothelial NAD(P)H oxidase-derived H2O2 down-regulates DHFR expression in response to angiotensin II, resulting in H4B deficiency and uncoupling of eNOS. This signaling cascade may represent a universal mechanism underlying eNOS dysfunction under pathophysiological conditions associated with oxidant stress.

Angiotensin II↗

PubMed1979

Appearance in confluent vascular endothelial cell monolayers of a specific cell surface protein (CSP-60) not detected in actively growing endothelial cells or in cell types growing in multiple layers.

The formation of a highly organized vascular and corneal endothelial cell monolayer is associated with the appearance of a 60,000-dalton cell surface protein (CSP-60) (30,000 daltons after reduction with dithiothreitol) which is not detectable in rapidly growing endothelial cells and in subconfluent cultures that do not yet exhibit the strict morphology of a confluent monolayer. It is also absent from vascular smooth muscle cells and from endothelial cultures that are maintained in the absence of fibroblast growth factor and grow on top of each other at confluence. After disorganization of cells in a confluent endothelial monolayer by urea, EDTA, or trypsin, CPS-60 is no longer exposed on the cell surface, but it reappears as soon as the cells readopt their characteristic two-dimensional configuration. This reorganization can be achieved in the presence of cycloheximide and despite removal of fibronectin by urea, EDTA, or trypsin. Maximal amounts of fibronectin and no CSP-60 are detected in subconfluent, but not yet organized, endothelial cultures or in endothelial cells that no longer form a monolayer of nonoverlapping cells at confluence. Likewise, cultures of vascular smooth muscle cells contain fibronectin but no CSP-60. These results suggest that CSP-60, rather than fibronectin, could be involved in the adoption of a monolayer configuration by confluent endothelial cells.

Aorta↗

PubMed2000

Vascular endothelial junction-associated molecule, a novel member of the immunoglobulin superfamily, is localized to intercellular boundaries of endothelial cells.

During the process of lymphocyte homing to secondary lymphoid organs, such as lymph nodes and tonsils, lymphocytes interact with and cross a specialized microvasculature, known as high endothelial venules. There is a great deal of information available about the first steps in the homing cascade, but molecular understanding of lymphocyte transmigration through the intercellular junctions of high endothelial venules is lacking. In analyzing expressed sequence tags from a cDNA library prepared from human tonsillar high endothelial cells, we have identified a cDNA encoding a novel member of the immunoglobulin superfamily. The protein, which we have termed VE-JAM ("vascular endothelial junction-associated molecule"), contains two extracellular immunoglobulin-like domains, a transmembrane domain, and a relatively short cytoplasmic tail. VE-JAM is prominently expressed on high endothelial venules but is also present on the endothelia of other vessels. Strikingly, it is highly localized to the intercellular boundaries of high endothelial cells. VE-JAM is most homologous to a recently identified molecule known as Junctional Adhesion Molecule, which is concentrated at the intercellular boundaries of both epithelial and endothelial cells. Because the Junctional Adhesion Molecule has been strongly implicated in the processes of neutrophil and monocyte transendothelial migration, an analogous function of VE-JAM during lymphocyte homing is plausible.

Amino Acid Sequence↗

PubMed1986

Immunocytochemical studies of endothelial cells in vivo. I. The presence of desmin only, or of desmin plus vimentin, or vimentin only, in the endothelial cells of different capillaries of the adult chicken.

It is currently believed that the intermediate filaments of endothelial cells contain vimentin subunits exclusively. This inference, however, is derived from studies of only a few types of endothelial cells. By double indirect immunofluorescence and immunoelectron microscopy, we have now examined the endothelial cells of the micro- and macrovasculature of a variety of tissues and organs of adult chicken in vivo for their content of desmin and vimentin. Endothelial cells of the peritubular capillary in the renal cortex, the hepatic sinusoid, and the splenic sinusoid were found to contain only desmin; those of the exocrine pancreas capillary contained both desmin and vimentin; and the endothelial cells of the macrovasculatures and of all the other microvasculatures examined, including the vasa recta of the renal medulla, contained only vimentin. Such heterogeneity suggests that different types of adult chicken endothelial cells may have different embryological origins. To the extent that desmin and vimentin intermediate filaments may be functionally distinct, these results also suggest that different capillary endothelial cells may have different functional properties.

Animals↗