endothelial function
Dotaz
Zobrazit nápovědu
ix, 123 s., [4] s. obr. příl. : il., tab., grafy ; 20 cm
- MeSH
- arterioskleróza MeSH
- ateroembolie MeSH
- cévní endotel MeSH
- inhibitory ACE MeSH
- kininy MeSH
- Publikační typ
- kongresy MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- angiologie
- MeSH
- cévní endotel patofyziologie patologie MeSH
- dilatace MeSH
- koronární nemoc MeSH
- lidé MeSH
- průchodnost cév MeSH
- ultrasonografie MeSH
- vazomotorický systém MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- srovnávací studie MeSH
Drugs. 1, ISSN 0012-6667 Supplement Vol. 53
44 s. : il. ; 26 cm
Endothelial cell (EC) glycocalyx (GLX) comprise a multicomponent layer of proteoglycans and glycoproteins. Alteration of its integrity contributes to chronic vascular inflammation and leads to the development of cardiovascular diseases. Myeloperoxidase (MPO), a highly abundant enzyme released by polymorphonuclear neutrophils, binds to the GLX and deleteriously affects vascular EC functions. The focus of this study was to elucidate the mechanisms of MPO-mediated alteration of GLX molecules, and to unravel subsequent changes in endothelial integrity and function. MPO binding to GLX of human ECs and subsequent internalization was mediated by cell surface heparan sulfate chains. Moreover, interaction of MPO, which is carrying a cationic charge, with anionic glycosaminoglycans (GAGs) resulted in reduction of their relative charge. By means of micro-viscometry and atomic force microscopy, we disclosed that MPO can crosslink GAG chains. MPO-dependent modulation of GLX structure was further supported by alteration of wheat germ agglutinin staining. Increased expression of ICAM-1 documented endothelial cell activation by both catalytically active and also inactive MPO. Furthermore, MPO increased vascular permeability connected with reorganization of intracellular junctions, however, this was dependent on MPO's catalytic activity. Novel proteins interacting with MPO during transcytosis were identified by proteomic analysis. Altogether, these findings provide evidence that MPO through interaction with GAGs modulates overall charge of the GLX, causing modification of its structure and thus affecting EC function. Importantly, our results also suggest a number of proteins interacting with MPO that possess a variety of cellular localizations and functions.
- MeSH
- cévní endotel MeSH
- endoteliální buňky MeSH
- lidé MeSH
- neutrofily MeSH
- peroxidasa * MeSH
- proteomika * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
American journal of cardiology. 10A, ISSN 0002-9149 Symposium Vol. 82
64S s. : il. ; 30 cm
- MeSH
- cévní endotel patofyziologie fyziologie účinky léků MeSH
- kardiovaskulární nemoci farmakoterapie MeSH
- Publikační typ
- kongresy MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- kardiologie
- angiologie
- MeSH
- cévní endotel účinky léků MeSH
- dospělí MeSH
- lidé MeSH
- simvastatin aplikace a dávkování farmakologie terapeutické užití MeSH
- srdeční selhání farmakoterapie patologie MeSH
- statiny farmakologie terapeutické užití MeSH
- superoxiddismutasa metabolismus MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- klinické zkoušky MeSH
Endoteliální glykokalyx (EG) je tenká vrstva na povrchu endotelu s širokým významem pro mikrocirkulaci a metabolismus tkání. Role EG je různorodá – funguje jako ochrana endotelu proti smykovému tření, které mediuje na intracelulární struktury endoteliálních buněk, umožňuje interakci krevních elementů a endotelu, brání rozvoji nekontrolované nástěnné trombózy a nadměrnému oxidačnímu působení radikálů. K dysfunkci EG může dojít částečnou nebo úplnou ztrátou jeho složek, což má za následek zhoršení vaskulární regulace a zvýšení vaskulární permeability. Narušení nebo dysfunkce EG jsou spojeny s patologickými stavy, jako je diabetes, chronická renální insuficience, zánětlivé stavy, sepse, hypernatremie, hypervolemie a ischemicko-reperfuzní poškození. Enzymy jako hyaluronidáza a metaloproteinázy degradují komponenty EG. Poškození EG vede k uvolňování rozpadových produktů do krevního oběhu, které lze detekovat. Existují i přímé metody vizualizace EG. Díky pokrokům ve studiu EG při transplantaci ledviny lze hodnotit komplexní vztah k této oblasti a dané klinické aspekty. Do budoucna může mít zkoumání potenciálních terapeutických možností s cílem ochrany EG dopady na lepší funkci a přežívání ledvinných štěpů. Cílem práce je shrnutí současného stavu problematiky a poukázání na význam EG u transplantace ledvin.
The endothelial glycocalyx (EG) is a thin layer on the surface of the endothelium that plays an important role for microcirculation and tissue metabolism. The role of EG is diverse – it acts as a protection of the endothelium against shear stress which is mediated on the intracellular structures of endothelial cells, allows the interaction of blood elements and endothelium, prevents the formation of uncontrolled thrombosis and excessive oxidative stress by free radicals. EG dysfunction can occur with partial or complete loss of its components, resulting in impaired vascular regulation and increased vascular permeability. Disruption or dysfunction of EG has been associated with disease states such as diabetes, chronic kidney disease, inflammatory conditions, sepsis, hypernatraemia, hypervolaemia and ischaemia/reperfusion injury. Enzymes such as hyaluronidase and metalloproteinases can degrade the components of EG. Damage to EG leads to the release of breakdown products into the bloodstream which can be detected. There are also direct methods of visualization of EG. Thanks to advances in the study of EG in kidney transplantation a comprehensive relationship in this field and specific clinical aspects can be assessed. In the future exploring potential therapeutic options to protect EG may have implications for better graft function and survival. The aim of this paper is to summarize the current knowledge and to point out the importance of EG in kidney transplantation.
Aim. The aim of this study was to assess coagulation markers of endothelial damage and examine new markers of endothelial activation such as matrix metalloproteinases (MMPs) in a group of healthy pregnant women. Matrix metalloproteinase (MMP)-2, in particular, plays a major role in the degradation of the extracellular matrix confirming its essential function in both the survival (angiogenesis) and death of endothelial cells. Detection of specific coagulation factors, mainly released from the vascular endothelium such as vWF, sTM (soluble thrombomodulin) and ePCR (endothelial protein C receptor) and factors dependent on endothelial activation such as t-PA and PAI-1, could provide information on possible endothelial dysfunction and help differentiate pregnant patients with an altered thrombotic state. Methods. Healthy pregnant women underwent complete assessment for endothelial damage (as vWF, vWF activity, sTM, ePCR, EMP, MMP-2, MMP-9 and TIMP-2) using the ELISA and other methods. Results and Conclusions. The results show that endothelial activation during pregnancy is different from that in other pathological conditions involving endothelial damage and typically characterized by higher levels of both coagulation endothelial markers and MMPs. In pregnancy, changes in extracellular matrix composition and matrix metalloproteinase activity also occur and promote vascular remodeling but, only in the uterus. Predisposing risk factors for epithelial dysfunction, and vascular mediators associated with vascular remodeling must be assessed from concentrations in whole blood. The levels of MMPs are not increased in the circulation and the local situation in the uterus cannot be monitored this way. However, MMP-2 processes and modulates the functions of many other vasoactive and pro-inflammatory molecules including adrenomedullin, big endothelin-1, calcitonin gene-related peptide, CCL7/MCP-3, CXCL12/SDF-1, galectin-3, IGFBP-3, IL-1 Beta, S100A8, and S100A9. These molecules represent new potential molecular markers of endothelial damage during pregnancy.
- MeSH
- biologické markery analýza MeSH
- cévní endotel fyziologie patofyziologie MeSH
- extracelulární matrix metabolismus MeSH
- koagulační faktory metabolismus MeSH
- komplikace těhotenství patofyziologie MeSH
- lidé MeSH
- matrixové metaloproteinasy metabolismus MeSH
- těhotenství fyziologie MeSH
- tkáňové inhibitory metaloproteinas metabolismus MeSH
- Check Tag
- lidé MeSH
- těhotenství fyziologie MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
