Syk expression in endothelial cells and their morphologic defects in embryonic Syk-deficient mice

Blood ◽  
2001 ◽  
Vol 98 (9) ◽  
pp. 2869-2871 ◽  
Author(s):  
Shigeru Yanagi ◽  
Ryoko Inatome ◽  
Junyi Ding ◽  
Hironori Kitaguchi ◽  
Victor L. J. Tybulewicz ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Function ◽  
Critical Role ◽  
Microscopic Analysis ◽  
Electron Microscopic ◽  
Vascular Integrity ◽  
Endothelial Cell Function ◽  
Deficient Mice

Abstract Mice deficient in the Syk tyrosine kinase showed severe petechiae in utero and died shortly after birth. The mechanism of this bleeding, however, remains unknown. Here it is shown that this bleeding is caused by morphologic defects of Syk-deficient endothelial cells during embryogenesis. Immunoblot and reverse transcriptase–polymerase chain reaction Northern blot analysis indicated that Syk is expressed in several endothelial cell lines. Immunocytochemical analysis also confirmed that Syk is expressed in the normal embryonic endothelial cells and is absent in Syk-deficient mice. Furthermore, electron microscopic analysis of Syk-deficient mice revealed an abnormal morphogenesis and a decreased number of endothelial cells. The results indicate a critical role for Syk in endothelial cell function and in maintaining vascular integrity in vivo.

scholarly journals Regulation of fibrinolysis by S100A10 in vivo

Blood ◽  
2011 ◽  
Vol 118 (11) ◽  
pp. 3172-3181 ◽  
Author(s):  
Alexi P. Surette ◽  
Patricia A. Madureira ◽  
Kyle D. Phipps ◽  
Victoria A. Miller ◽  
Per Svenningsson ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Function ◽  
Blood Clot ◽  
Critical Role ◽  
Receptor Protein ◽  
Null Mouse ◽  
Wild Type ◽  
Endothelial Cell Function

AbstractEndothelial cells form the inner lining of vascular networks and maintain blood fluidity by inhibiting blood coagulation and promoting blood clot dissolution (fibrinolysis). Plasmin, the primary fibrinolytic enzyme, is generated by the cleavage of the plasma protein, plasminogen, by its activator, tissue plasminogen activator. This reaction is regulated by plasminogen receptors at the surface of the vascular endothelial cells. Previous studies have identified the plasminogen receptor protein S100A10 as a key regulator of plasmin generation by cancer cells and macrophages. Here we examine the role of S100A10 and its annexin A2 binding partner in endothelial cell function using a homozygous S100A10-null mouse. Compared with wild-type mice, S100A10-null mice displayed increased deposition of fibrin in the vasculature and reduced clearance of batroxobin-induced vascular thrombi, suggesting a role for S100A10 in fibrinolysis in vivo. Compared with wild-type cells, endothelial cells from S100A10-null mice demonstrated a 40% reduction in plasminogen binding and plasmin generation in vitro. Furthermore, S100A10-deficient endothelial cells demonstrated impaired neovascularization of Matrigel plugs in vivo, suggesting a role for S100A10 in angiogenesis. These results establish an important role for S100A10 in the regulation of fibrinolysis and angiogenesis in vivo, suggesting S100A10 plays a critical role in endothelial cell function.

scholarly journals Sodium and potassium regulate endothelial phospholipase C-γ and Bmx

2014 ◽  
Vol 307 (1) ◽  
pp. F58-F63 ◽  
Author(s):  
Wei-Zhong Ying ◽  
Kristal J. Aaron ◽  
Paul W. Sanders
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Tyrosine Kinase ◽  
Phospholipase C ◽  
Intracellular Signaling ◽  
Cell Function ◽  
Pleckstrin Homology Domain ◽  
Endothelial Cell Function ◽  
Salt Diet

The amount of Na+ and K+ in the diet promotes significant changes in endothelial cell function. In the present study, a series of in vitro and in vivo experiments determined the role of Na+ and K+ in the regulation of two pleckstrin homology domain-containing intracellular signaling molecules, phospholipase C (PLC)-γ1 and epithelial and endothelial tyrosine kinase/bone marrow tyrosine kinase on chromosome X (Bmx), and agonist-generated Ca2+ signaling in the endothelium. Extracellular K+ concentration regulated the levels of activated PLC-γ1, Bmx, and carbachol-stimulated intracellular Ca2+ mobilization in human endothelial cells. Additional experiments confirmed that high-conductance Ca2+-activated K+ channels and phosphatidylinositol 3-kinase mediated these effects. The content of Na+ and K+ in the diet also regulated Bmx levels in endothelial cells and activated PLC-γ1 levels in rats in vivo. The effects of dietary K+ on Bmx were more pronounced in rats fed a high-salt diet compared with rats fed a low-salt diet. These experiments elucidated an endothelial cell signaling mechanism regulated by electrolytes, further demonstrating an integral relationship between endothelial cell function and dietary Na+ and K+ content.

scholarly journals The effect of quercetin on endothelial cells is modified by heterocellular interactions

2020 ◽  
Vol 11 (5) ◽  
pp. 3916-3925
Author(s):  
Sarka Tumova ◽  
Michael J. Houghton ◽  
Gary Williamson
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Single Cell ◽  
Cell Function ◽  
Cell Interactions ◽  
Cell Type ◽  
Endothelial Cell Function ◽  
Single Cell Type ◽  
Cell Cell

Single cell-type models are useful for determining mechanisms, but in vivo, cell–cell interactions are important, and neighbouring cells can impact endothelial cell function.

An Electron Microscopic Study of Platelet Thrombus Formation in the Rabbit with Particular Regard to 5-Hydroxytryptamine Release

1967 ◽  
Vol 18 (03/04) ◽  
pp. 592-604 ◽  
Author(s):  
H. R Baumgartner ◽  
J. P Tranzer ◽  
A Studer
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Vessel Wall ◽  
Thrombus Formation ◽  
Endothelial Damage ◽  
Electron Microscopic ◽  
Rabbit Ear ◽  
Basement Lamina ◽  
Platelet Thrombus

SummaryElectron microscopic and histologic examination of rabbit ear vein segments 4 and 30 min after slight endothelial damage have yielded the following findings :1. Platelets do not adhere to damaged endothelial cells.2. If the vessel wall is denuded of the whole endothelial cell, platelets adhere to the intimai basement lamina as do endothelial cells.3. The distance between adherent platelets as well as endothelial cells and intimai basement lamina measures 10 to 20 mµ, whereas the distance between aggregated platelets is 30 to 60 mµ.4. 5-hydroxytryptamine (5-HT) is released from platelets during viscous metamorphosis at least in part as 5-HT organelles.It should be noted that the presence of collagen fibers is not necessary for platelet thrombus formation in vivo.

Disruption of endothelial Pfkfb3 ameliorates diet-induced murine insulin resistance

2021 ◽  
Author(s):  
Qiuhua Yang ◽  
Jiean Xu ◽  
Qian Ma ◽  
Zhiping Liu ◽  
Yaqi Zhou ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Endothelial Cells ◽  
High Fat Diet ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Endothelial Inflammation ◽  
Glucose Clearance ◽  
Deficient Mice

Overnutrition-induced endothelial inflammation plays a crucial role in high fat diet (HFD)-induced insulin resistance in animals. Endothelial glycolysis plays a critical role in endothelial inflammation and proliferation, but its role in diet-induced endothelial inflammation and subsequent insulin resistance has not been elucidated. PFKFB3 is a critical glycolytic regulator, and its increased expression has been observed in adipose vascular endothelium of C57BL/6J mice fed with HFD in vivo, and in palmitate (PA)-treated primary human adipose microvascular endothelial cells (HAMECs) in vitro. We generated mice with Pfkfb3 deficiency selective for endothelial cells to examine the effect of endothelial Pfkfb3 in endothelial inflammation in metabolic organs and in the development of HFD-induced insulin resistance. EC Pfkfb3-deficient mice exhibited mitigated HFD-induced insulin resistance, including decreased body weight and fat mass, improved glucose clearance and insulin sensitivity, and alleviated adiposity and hepatic steatosis. Mechanistically, cultured PFKFB3 knockdown HAMECs showed decreased NF-κB activation induced by PA, and consequent suppressed adhesion molecule expression and monocyte adhesion. Taken together, these results demonstrate that increased endothelial PFKFB3 expression promotes diet-induced inflammatory responses and subsequent insulin resistance, suggesting that endothelial metabolic alteration plays an important role in the development of insulin resistance.

High Glucose Alters Endothelial Cell Response to Shear Stress

2009 ◽  
Author(s):  
Steven F. Kemeny ◽  
Alisa Morss Clyne
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Blood Vessels ◽  
Cell Mechanics ◽  
High Glucose ◽  
Fluid Shear Stress ◽  
Cell Function ◽  
Focal Adhesions ◽  
Endothelial Cell Function

Endothelial cells line the walls of all blood vessels, where they maintain homeostasis through control of vascular tone, permeability, inflammation, and the growth and regression of blood vessels. Endothelial cells are mechanosensitive to fluid shear stress, elongating and aligning in the flow direction [1–2]. This shape change is driven by rearrangement of the actin cytoskeleton and focal adhesions [2]. Hyperglycemia, a hallmark of diabetes, affects endothelial cell function. High glucose has been shown to increase protein kinase C, formation of glucose-derived advanced glycation end-products, and glucose flux through the aldose reductase pathway within endothelial cells [3]. These changes are thought to be related to increased reactive oxygen species production [4]. While endothelial cell mechanics have been widely studied in healthy conditions, many disease states have yet to be explored. Biochemical alterations related to high glucose may alter endothelial cell mechanics.

scholarly journals Targeting QKI-7 in vivo restores endothelial cell function in diabetes

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Chunbo Yang ◽  
Magdalini Eleftheriadou ◽  
Sophia Kelaini ◽  
Thomas Morrison ◽  
Marta Vilà González ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Function ◽  
Vascular Endothelial Cell ◽  
Vascular Complications ◽  
Limb Ischemia ◽  
Limb Amputation ◽  
Diabetic Patients ◽  
Ips Cell ◽  
Endothelial Cell Function

Abstract Vascular endothelial cell (EC) dysfunction plays a key role in diabetic complications. This study discovers significant upregulation of Quaking-7 (QKI-7) in iPS cell-derived ECs when exposed to hyperglycemia, and in human iPS-ECs from diabetic patients. QKI-7 is also highly expressed in human coronary arterial ECs from diabetic donors, and on blood vessels from diabetic critical limb ischemia patients undergoing a lower-limb amputation. QKI-7 expression is tightly controlled by RNA splicing factors CUG-BP and hnRNPM through direct binding. QKI-7 upregulation is correlated with disrupted cell barrier, compromised angiogenesis and enhanced monocyte adhesion. RNA immunoprecipitation (RIP) and mRNA-decay assays reveal that QKI-7 binds and promotes mRNA degradation of downstream targets CD144, Neuroligin 1 (NLGN1), and TNF-α-stimulated gene/protein 6 (TSG-6). When hindlimb ischemia is induced in diabetic mice and QKI-7 is knocked-down in vivo in ECs, reperfusion and blood flow recovery are markedly promoted. Manipulation of QKI-7 represents a promising strategy for the treatment of diabetic vascular complications.

Effect of anti-oxidative enzyme gene-transfer on endothelial cell function of apolipoprotein-E deficient mice

2006 ◽  
Vol 45 (3) ◽  
pp. e73-e74
Author(s):  
P-J. Guns ◽  
T. Van Assche ◽  
W. Verreth ◽  
P. Fransen ◽  
B. Mackness ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Gene Transfer ◽  
Apolipoprotein E ◽  
Cell Function ◽  
Oxidative Enzyme ◽  
Endothelial Cell Function ◽  
Enzyme Gene ◽  
Deficient Mice

Peroxynitrite increases iNOS through NF-κB and decreases prostacyclin synthase in endothelial cells

2002 ◽  
Vol 282 (2) ◽  
pp. C395-C402 ◽  
Author(s):  
Christy-Lynn M. Cooke ◽  
Sandra T. Davidge
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Vascular Reactivity ◽  
Cell Function ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Cell Nuclei ◽  
Endothelial Cell Function ◽  
Protein Mass ◽  
Prostacyclin Synthase

Peroxynitrite, a marker of oxidative stress, is elevated in conditions associated with vascular endothelial cell dysfunction, such as atherosclerosis, preeclampsia, and diabetes. However, the effects of peroxynitrite on endothelial cell function are not clear. The endothelium-derived enzymes nitric oxide synthase (NOS) and prostaglandin H synthase (PGHS) mediate vascular reactivity and contain oxidant-sensitive isoforms (iNOS and PGHS-2) that can be induced by nuclear factor (NF)-κB activation. We investigated the effect(s) of peroxynitrite on NOS and PGHS pathways in endothelial cells. We hypothesized that peroxynitrite will increase levels of iNOS and PGHS-2 through activation of NF-κB. Western immunoblots of endothelial cells show that 3-morpholinosydnonimine (SIN-1; 0.5 mM), a peroxynitrite donor, increased iNOS protein mass, which can be inhibited by pyrroline dithiocarbamate (an NF-κB inhibitor) (167 ± 24.2 vs. 78 ± 19%, P < 0.05, n = 6). SIN-1 treatment also significantly increased NF-κB translocation into endothelial cell nuclei (135 ± 10%, P < 0.05). Endothelial NOS, PGHS-1, and PGHS-2 protein levels were not altered by SIN-1. However, prostacyclin synthase protein mass, but not mRNA, was significantly reduced in SIN-1-treated endothelial cells (78 ± 8.9%, P < 0.05). Our results illustrate novel mechanisms through which peroxynitrite may modulate vascular endothelial function.

scholarly journals Up-regulation of the Notch ligand Delta-like 4 inhibits VEGF-induced endothelial cell function

Blood ◽  
2006 ◽  
Vol 107 (3) ◽  
pp. 931-939 ◽  
Author(s):  
Cassin Kimmel Williams ◽  
Ji-Liang Li ◽  
Matilde Murga ◽  
Adrian L. Harris ◽  
Giovanna Tosato
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Function ◽  
Umbilical Vein ◽  
Endothelial Cell Proliferation ◽  
Vegf Receptor ◽  
Endothelial Cell Function ◽  
Notch Ligand ◽  
Neuropilin 1 ◽  
Umbilical Vein Endothelial Cells

AbstractDelta-like 4 (Dll4), a membrane-bound ligand for Notch1 and Notch4, is selectively expressed in the developing endothelium and in some tumor endothelium, and it is induced by vascular endothelial growth factor (VEGF)-A and hypoxia. Gene targeting studies have shown that Dll4 is required for normal embryonic vascular remodeling, but the mechanisms underlying Dll4 regulatory functions are currently not defined. In this study, we generated primary human endothelial cells that overexpress Dll4 protein to study Dll4 function and mechanism of action. Human umbilical vein endothelial cells retrovirally transduced with Dll4 displayed reduced proliferative and migratory responses selectively to VEGF-A. Expression of VEGF receptor-2, the principal signaling receptor for VEGF-A in endothelial cells, and coreceptor neuropilin-1 was significantly decreased in Dll4-transduced endothelial cells. Consistent with Dll4 signaling through Notch, expression of HEY2, one of the transcription factors that mediates Notch function, was significantly induced in Dll4-overexpressing endothelial cells. The γ-secretase inhibitor L-685458 significantly reconstituted endothelial cell proliferation inhibited by immobilized extracellular Dll4 and reconstituted VEGFR2 expression in Dll4-overerexpressing endothelial cells. These results identify the Notch ligand Dll4 as a selective inhibitor of VEGF-A biologic activities down-regulating 2 VEGF receptors expressed on endothelial cells and raise the possibility that Dll4 may be exploited therapeutically to modulate angiogenesis.

Sign in / Sign up

Export Citation Format

Share Document