ix, 123 s., [4] s. obr. příl. : il., tab., grafy ; 20 cm
- MeSH
- Arteriosclerosis MeSH
- Embolism, Cholesterol MeSH
- Endothelium, Vascular MeSH
- Angiotensin-Converting Enzyme Inhibitors MeSH
- Kinins MeSH
- Publication type
- Congress MeSH
- Conspectus
- Patologie. Klinická medicína
- NML Fields
- angiologie
- MeSH
- Endothelium, Vascular physiopathology pathology MeSH
- Dilatation MeSH
- Coronary Disease MeSH
- Humans MeSH
- Vascular Patency MeSH
- Ultrasonography MeSH
- Vasomotor System MeSH
- Check Tag
- Humans MeSH
- Publication type
- Comparative Study MeSH
Drugs. 1, ISSN 0012-6667 Supplement Vol. 53
44 s. : il. ; 26 cm
Angiotensin konvertující enzym (ACE) a možnost jeho inhibice jsou důležité v potlačení tvorby negativně působícího angiotensinu II a potenciaci vlivu bradykininu. ACE je primárně lokalizován v tkáních a orgánech, zejména v endoteliích, mozku, srdci, ledvinách a zánětlivých buňkách, pouze jeho malá část cirkuluje. V souladu s tímto se inhibice tkáňového ACE stala terapeutickým cílem v léčbě řady kardiovaskulárních nemocí: arteriální hypertenze, chronické srdeční nedostatečnosti a nejnověji se zdá, že i v indikaci aterosklerotického poškození tepenné stěny obecně. Poslední data podporují teorii, že inhibitory ACE zlepšují prognózu nemocných s kardiovaskulárními chorobami tím, že snižují o více než 20í i renální nedostatečnosti. Mechanizmy, které by mohly být za tento benefit zodpovědné, jsou kromě snížení krevního tlaku a prevence remodelace i zlepšení funkce endotelu, myokardiální perfuze a příznivé ovlivnění fibrinolytické kapacity organizmu.
Angiotensin converting enzyme (ACE) and the possibility of its inhibition is important for diminishing the release of the pressor substance angiotensin II and preserving the benefit of bradykinin. ACE is primarily localized in various tissues and organs, most notably in endothelial cells, the brain, the heart, the kidney and inflammatory cells, only smaller part is circulating. Accordingly with this the inhibition of tissue-ACE has become a therapeutic goal in the treatment of many cardiovascular (CV) disorders: arterial hypertension, cardiac insufficiency and atherosclerotic vasculopathy. Recent data support the concept that ACE-inhibitors with high tissue-affinity improve the prognosis of patients with CV diseases by reducing the risk of myocardial infarction, stroke, chronic heart and renal failure by more than 20%. Mechanisms that may contribute to these beneficial effects include beside lowering of blood pressure and prevention of remodelling also improvement of endothelial function, myocardial perfusion and fibrinolytic balance.
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
- Endothelium, Vascular MeSH
- Endothelial Cells MeSH
- Humans MeSH
- Neutrophils MeSH
- Peroxidase * MeSH
- Proteomics * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- MeSH
- Platelet Adhesiveness physiology MeSH
- Arteriosclerosis etiology pathology therapy MeSH
- Endothelium, Vascular physiology pathology MeSH
- Cardiovascular Diseases pathology MeSH
- Coronary Disease etiology pathology MeSH
- Humans MeSH
- Nitric Oxide pharmacology MeSH
- Vascular Patency MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
- MeSH
- Arteriosclerosis drug therapy MeSH
- Endothelium, Vascular drug effects MeSH
- Adult MeSH
- Fenofibrate therapeutic use MeSH
- Hypercholesterolemia drug therapy pathology MeSH
- Hypertriglyceridemia drug therapy pathology MeSH
- Hypolipidemic Agents therapeutic use MeSH
- Humans MeSH
- Ultrasonography methods MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
