Introduction
The molecular structure determines virulence
Signaling pathways of LPS in endothelial cells
LPS activates endothelial cells
Endothelial markers | Ligands | Effects |
---|---|---|
Endoglin | TGF-β | Essential for angiogenesis |
vWF | Factor VIII, platelet glycoprotein, heparin, and collagen | Regulating angiogenesis, proliferation and migration as well as Ang-2 release |
ICAM-1 | ICAM-1 | Modulating leukocyteadhesion and movement on endothelial cells |
VCAM-1 | VLA-4 integrin | Modulating leukocyteadhesion and movement on endothelial cells |
PECAM-1 | CD31 | Promoting endothelial intercellular junction to enhance endothelial barrier properties. modulate leukocyte adhesion and movement on endothelial cells |
E-selectin | Sialyl-Lewis X antigen and other carbohydrates | Modulating leukocyte movement on endothelial cells |
P-selectin | Carbohydrate determinants on selectin ligands | Regulating leukocyte adhesion and movement on endothelial cells |
VEGFR-1(Flt-1) | VEGF | Stimulating endothelial cell migration, hyperpermeability, and angiogenesis |
VEGFR-2 (Flk-1) | VEGF | Promoting certain cancers progression |
Tie-2 | Angiopoietins | Regulating angiogenesis and permeability of endothelial cells |
ACE | Angiotensin | Catalyzing the conversion of angiotensin I to angiotensin II to induce vasoconstriction and increase vascular permeability |
ANGPTLs | Leukocyte immunoglobulin-like receptors | Regulating angiogenesis and some may exhibit other functions |
LPS induces endothelial injury
Markers | Effects | Clinical implications |
---|---|---|
Occludin | Occludin is a major component of the tight junction of epithelial and/or endothelial barriers | Occludin level is increased in numerous pathologic conditions, including HIV, cancer, neuroinflammation and sepsis |
Syndecan-1 | Syndecan-1 is released in endothelial glycocalyx damage | Syndecan-1 levels in circulation are associated with severity of sepsis, acute kidney injury, need for intubation, and mortality |
Endocan | Endocan is a soluble dermatan sulfate proteoglycan in endothelial cells | Endocan can regulate major processes, such as cell adhesion, in inflammatory disorders and tumor progression |
claudin-5 | Claudin-5 can modulate the permeability of tight junctions | Levels of claudin-5 in serum is to correlate with severe plasma leakage |
cadherin-5 | Cadherin-5 is a main component of adherens junction | Loss of vascular endothelial cadherin results in increased permeability |
ZO-1 | ZO-1 is a component of tight junction proteins | ZO-1 is associated with inflammation and cancer |
TF | Exposure of TF attract interaction with the FVII and FX that activate both coagulation cascades | TF can activate both coagulation cascades and increase vascular permeability |
PAI-1 | As the main negative regulator of plasminogen activation, PAI-1 is an essential factor in regulation of the physiological balance between thrombosis and fibrinolysis | High PAI-1 levels are associated with many cardiovascular diseases |
Antithrombin | Antithrombin is the active anticoagulant operative during heparin therapy to inhibit thrombin, factor 10a, and, less efficiently, factors 9a and 11a | Heparin-like molecules are synthesized by endothelial cells and interact with AT on the vessel wall to inhibit coagulation |
Thrombomodulin | Thrombomodulin is an endothelial transmembrane glycoprotein that possess a central modulatory role in the natural anticoagulant system | Thrombomodulin can blocks thrombin to inactivate the pro-coagulant signaling and the downstream pro-inflammatory responses |
Angiopoietin-1/2 | Angiopoietin-1 and 2 (Ang1, Ang2) are important mediators of angiogenesis | Perturbation of Angiopoietin-1/2 leads to various pathological conditions, such as inflammation, tumor and restenosis |
sICAM-1 | sICAM-1 can mediate leukocyte migration and adhesion to target structures by binding to the leukocyte adhesion receptor | sICAM-1 is upregulated in endothelial dysfunction and promotes an inflammatory response |
sVCAM-1 | sVCAM-1 plays an important role in the adhesion and migration of leukocytes from blood to vascular intima | sVCAM-1 are considered to be markers of endothelial cell activity or injury |
sFlt-1 | sFlt-1 is a soluble antagonist of VEGF with an essential effect of maintaining the balance of vascular growth | sFlt-1 is associated with markers of inflammation, endothelial function, and myocardial stress or injury |
sE-Selectin | E-selectin is a recognized marker of endothelial activation | sE-selectin expression by endothelial cells is crucial for leukocyte recruitment during the inflammatory response |