scholarly journals Feedback Regulation of Endothelial Cell Surface Plasmin Generation by PKC-dependent Phosphorylation of Annexin A2

2010 ◽  
Vol 286 (17) ◽  
pp. 15428-15439 ◽  
Author(s):  
Kai-Li He ◽  
Guangzhi Sui ◽  
Huabao Xiong ◽  
M. Johan Broekman ◽  
Bihui Huang ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Surface ◽  
Feedback Regulation ◽  
Annexin A2 ◽  
Endothelial Cell Surface

scholarly journals Dysfunction of annexin A2 contributes to hyperglycaemia-induced loss of human endothelial cell surface fibrinolytic activity

2013 ◽  
Vol 109 (06) ◽  
pp. 1070-1078 ◽  
Author(s):  
Zhanyang Yu ◽  
Xiang Fan ◽  
Ning Liu ◽  
Min Yan ◽  
Zhong Chen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Surface ◽  
Protein Expression ◽  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Annexin A2 ◽  
Tissue Type ◽  
Endothelial Cell Surface ◽  
Pai 1

SummaryHyperglycaemia impairs fibrinolytic activity on the surface of endothelial cells, but the underlying mechanisms are not fully understood. In this study, we tested the hypothesis that hyperglycaemia causes dysfunction of the endothelial membrane protein annexin A2, thereby leading to an overall reduction of fibrinolytic activity. Hyperglycaemia for 7 days significantly reduced cell surface fibrinolytic activity in human brain microvascular endothelial cells (HBMEC). Hyperglycaemia also decreased tissue type plasminogen activator (t-PA), plasminogen, and annexin A2 mRNA and protein expression, while increasing plasminogen activator inhibitor-1 (PAI-1). No changes in p11 mRNA or protein expression were detected. Hyperglycaemia significantly increased AGE-modified forms of total cellular and membrane annexin A2. The hyperglycemia-associated reduction in fibrinolytic activity was fully restored upon incubation with recombinant annexin A2 (rA2), but not AGE-modified annexin A2 or exogenous t-PA. Hyperglycaemia decreased t-PA, upregulated PAI-1 and induced AGE-related disruption of annexin A2 function, all of which contributed to the overall reduction in endothelial cell surface fibrinolytic activity. Further investigations to elucidate the underlying molecular mechanisms and pathophysiological implications of A2 derivatisation might ultimately lead to a better understanding of mechanisms of impaired vascular fibrinolysis, and to development of new interventional strategies for the thrombotic vascular complications in diabetes.

scholarly journals Annexin A2 in Fibrinolysis, Inflammation and Fibrosis

2021 ◽  
Vol 22 (13) ◽  
pp. 6836
Author(s):  
Hana I. Lim ◽  
Katherine A. Hajjar
Keyword(s):  
Cell Surface ◽  
Tissue Injury ◽  
Critical Role ◽  
Annexin A2 ◽  
Hemorrhagic Disease ◽  
Membrane Repair ◽  
Endothelial Cell Surface ◽  
Human Disorders ◽  
A Cell ◽  
Organ Fibrosis

As a cell surface tissue plasminogen activator (tPA)-plasminogen receptor, the annexin A2 (A2) complex facilitates plasmin generation on the endothelial cell surface, and is an established regulator of hemostasis. Whereas A2 is overexpressed in hemorrhagic disease such as acute promyelocytic leukemia, its underexpression or impairment may result in thrombosis, as in antiphospholipid syndrome, venous thromboembolism, or atherosclerosis. Within immune response cells, A2 orchestrates membrane repair, vesicle fusion, and cytoskeletal organization, thus playing a critical role in inflammatory response and tissue injury. Dysregulation of A2 is evident in multiple human disorders, and may contribute to the pathogenesis of various inflammatory disorders. The fibrinolytic system, moreover, is central to wound healing through its ability to remodel the provisional matrix and promote angiogenesis. A2 dysfunction may also promote tissue fibrogenesis and end-organ fibrosis.

scholarly journals Surface charge distribution on the endothelial cell of liver sinusoids.

1984 ◽  
Vol 99 (2) ◽  
pp. 639-647 ◽  
Author(s):  
L Ghitescu ◽  
A Fixman
Keyword(s):  
Endothelial Cell ◽  
Cell Surface ◽  
Liver Sinusoid ◽  
Electron Microscopic ◽  
Coated Pits ◽  
Endothelial Cell Surface ◽  
Liver Sinusoids ◽  
Surface Charge Distribution ◽  
Cationic Residues

The topography of the charged residues on the endothelial cell surface of liver sinusoid capillaries was investigated by using electron microscopic tracers of different size and charge. The tracers used were native ferritin (pl 4.2-4.7) and its cationized (pl 8.4) and anionized (pl 3.7) derivatives, BSA coupled to colloidal gold (pl of the complex 5.1), hemeundecapeptide (pl 4.85), and alcian blue (pl greater than 10). The tracers were either injected in vivo or perfused in situ through the portal vein of the mouse liver. In some experiments, two tracers of opposite charge were sequentially perfused with extensive washing in between. The liver was processed for electron microscopy and the binding pattern of the injected markers was recorded. The electrostatic nature of the tracer binding was assessed by perfusion with high ionic strength solutions, by aldehyde quenching of the plasma membrane basic residues, and by substituting the cell surface acidic moieties with positively charged groups. Results indicate that the endothelial cells of the liver sinusoids expose on their surface both cationic and anionic residues. The density distribution of these charged groups on the cell surface is different. While the negative charge is randomly and patchily scattered all over the membrane, the cationic residues seem to be accumulated in coated pits. The charged groups co-exist in the same coated pit and bind the opposite charged macromolecule. It appears that the fixed positive and negative charges of the coated pit glycocalyx are mainly segregated in space. The layer of basic residues is located at 20-30-nm distance of the membrane, while most of the negative charges lie close to the external leaflet of the plasmalemma.

The ultrastructural basis of endothelial cell surface functions

Biorheology ◽  
1984 ◽  
Vol 21 (1-2) ◽  
pp. 155-170 ◽  
Author(s):  
Una S. Ryan ◽  
James W. Ryan
Keyword(s):  
Endothelial Cell ◽  
Cell Surface ◽  
Endothelial Cell Surface

scholarly journals Leukocyte adhesion is governed by endolysosomal two pore channel 2 (TPC2)

2021 ◽  
Author(s):  
Jonas Goretzko ◽  
Nicole Heitzig ◽  
Katharina Thomas ◽  
Einar Kleinhans Krogsaeter ◽  
Johannes Nass ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Surface ◽  
Leukocyte Adhesion ◽  
Leukocyte Recruitment ◽  
Pore Channel ◽  
Initial Contact ◽  
Surface Receptors ◽  
Endothelial Cell Surface ◽  
Late Endosomes ◽  
Endothelial Functions

In response to pro-inflammatory challenges including pathogenic attack and tissue damage, the endothelial cell surface is rearranged to present leukocyte-engaging cell surface receptors. The initial contact needed for leukocyte tethering and rolling is mediated via adhesion demand-driven exocytosis of Weibel-Palade bodies (WPB) that contain the leukocyte receptor P-selectin together with the stabilizing co-factor CD63. We found that diminished expression of the endolysosomal non-selective cation channel TPC2 or inhibition of TPC2-mediated Ca2+-release via trans-Ned 19 led to reduced endolysosomal Ca2+ efflux, and blocked transfer of CD63 from late endosomes/lysosomes (LEL) to WPB, and a concomitant loss of P-selectin on the endothelial cell surface. Accordingly, P-selectin-mediated leukocyte recruitment to trans-Ned 19-treated HUVEC under flow was significantly reduced without disturbing VWF exocytosis. Our findings establish the endolysosome-related TPC2 Ca2+ channel as a key element in the maintenance of proper endothelial functions and a potential pharmacological target in the control of inflammatory leukocyte recruitment.

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