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a|rytmia – [g - datasolution.sk

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aj gény pre expresiu svojho vlastného inhibítora (IKK), čo spätne inhibuje jeho aktiváciu<br />

(autoregulačný systém). Jeho úloha v rozvoji atero<strong>sk</strong>lerózy je teda veľmi komplexná a integračná.<br />

PPARb/d sú exprimované v mnohých tkanivách; pp. kontrolujú adipogenézu.<br />

Relat. riziko vzniku kardiova<strong>sk</strong>ulárnej choroby moţno určiť vyšetrením hsCRP a pomeru celkového<br />

cholesterolu a HDL-cholesterolu.<br />

<strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><br />

Tab.: Relatívne riziko koronárnej príhody určené podľa pomeru celkový<br />

cholesterol/HDL-C (TC/HDL) a koncentrácie bazálnej hodnoty CRP<br />

<strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><br />

TC/HDL<br />

Kvintily hs-CRP (mg/l)<br />

<strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><br />

Kvintily Muţi Ţeny 1 2 3 4 5<br />

<strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong>-<strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><br />

( 5,5 > 5,8 4,2 5,0 6,0 7,2 8,7<br />

<strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong><strong>–</strong>-<br />

V procese aterogenézy moţno rozlíšiť niekoľko štádií: 1. lézia endotelu; 2. hromadenie buniek v<br />

intime tepien; 3. tvorba zloţiek spojivového tkaniva v intime; 4. akumulácia lipidov v stene ciey; 5.<br />

vznik komplikácií.<br />

1. Lézia endotelu <strong>–</strong> endotel sa pokladá za vysoko metabolicky aktívny ,,orgán― s hmotnosťou ~ 1,5<br />

kg a mnohopočetnými funkciami. Dôleţitá je jeho bariérová, antitrombogénna a sekrečná funkcia.<br />

Endotelové bunky uvoľňujú viaceré vazodilatačne a vazokonstrikčne pôsobiace látky, medzi kt. je za<br />

normálnych podmienok rovonováha. Porušenie tejto rovnováhy v prospech vazokonstrikčných<br />

faktorov môţe mať za následok kontrakciu hladkej svaloviny ciev a ischémiu. Následná hypoxia<br />

zniţuje uvoľňovanie EDRF (endothelium derived relaxing factor, NO) a jeho inaktiváciu pôsobením<br />

voľných radikálov kyslíka. Dôkazom toho je napr. paradoxná vazokonstrikcia atero<strong>sk</strong>lerotických<br />

tepien po intraartériovej aplikácii acetylcholínu (Furchgott a Zawad<strong>sk</strong>i, 1993). Vazodilatačnej<br />

odpovedi cievy na acetylcholín zabraňuje aj sama hypercholesterolémia.<br />

Intaktný endotel pôsobí ako selektívna protitrombogénna bariéra. Endotelové bunky produkujú<br />

prostaglandín PGI 2 , kt. inhibujú agregáciu trombocytov. Ďalej uvoľňujú relaxačný faktor EDRF s<br />

vazodilatačným pôsobením, ako aj látku podobnú heparínu, kt. potláča rast hladkých svalových<br />

buniek. Endotelové bunky však môţu produkovať aj prokoagulačné a ďalšie faktory a<br />

vazokonstrikčné látky, ako je endotelín, kt. majú proaterogénny účinok.<br />

V endoteli sa tvoria aj rastové faktory a adhezívne látky (→endotel). Pri rozvoji a. nastáva porucha<br />

funkcie endotelu ešte pred vznikom histol. dokázateľných zmien. Pri a. sa v cievnom endoteli zistila<br />

zvýšená syntéza endotelínu a ďalších látok vyvolávajúcich kontrakciu myocytov. Zvýšené<br />

uvoľňovanie endotelínu zvyšujú aj oxidované LDL, kt. môţu priamo viazať EDRF(NO), a tým vyvolať<br />

vazokonstrikciu.<br />

Poškodenie endotelu má za následok ka<strong>sk</strong>ádu bunkových dejov, kt. majú charakter parakrinnej<br />

výmeny medzi jednotlivými bunkovými typmi cievnej steny a vyúsťujú do atero<strong>sk</strong>lerotickej lézie <strong>–</strong><br />

atero<strong>sk</strong>lerotického plátu.

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