Asimetrični dimetilarginin kao posrednik vaskularne disfunkcije u cirozi

master's thesis

• Title (english): Asymmetric dimethylarginine: mediator of vascular dysfunction in cirrhosis
• Author: Egon Kruezi
• Mentor: Anna Mrzljak (mentor)
• Committee member: Jasenka Markeljević (predsjednik povjerenstva)
• Committee member: Anna Mrzljak (član povjerenstva)
• Committee member: Tomislav Letilović (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Internal Medicine); Zagreb
• Defense date and country: 2017-07-14, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine

Abstract

Asimetrični dimetilarginin (ADMA) endogeni je inhibitor skupine enzima koji sudjeluju u sintezi u dušikovog oksida (NO), molekule sa dokazanim vazodilatacijskim učinkom, zbog čega je važan u patofiziologiji procesa vezanih uz endotel krvnih žila. Patološki vaskularni fenomeni vidljivi u cirozi jetre poput portalne hipertenzije, hiperdinamičke cirkulacije i hepatorenalnog sindroma smatraju se povezani sa promijenjenim vrijednostima ADMA i njenim utjecajem na sintezu NO.
Cilj ove studije je... More istražiti razlike u serumskim koncentracija asimetričnog dimetil arginina u bolesnika s cirozom jetre i utvrditi njegov odnos prema stadijima težine bolesti jetre. Ovo presječno istraživanje provedeno je na 90 odrasla bolesnika predominatno s cirozom jetre alkoholne etiologije u različitim stadijima jetrene bolesti definiranih temeljem Child-Pugh i MELD(Na) skora. Naši rezultati ukazuju da koncentracija ADMA-e u pojedinim skupinama iznosi za CP-A=0,73 ug/l, CP-B=0,80 ug/l, CP-C=0,91 ug/l. Iako su u našem istraživanju nominalno niže vrijednosti AMDA-e (0,73 ug/l) zabilježene kod bolesnika u CP-A kompenziranom stadiju bolesti, a više (0.87 ug/L) kod bolesnika u CP-B+C dekompenziranom stadiju, između skupina nije postignuta statistički značajna razlika (p=0,207). Naši podaci ukazuju da postoji slaba pozitivna korelacija između koncentracije ADMA-e u serumu i pojedinih stadija težine bolesti temeljem CP klasifikacije (r=0.284, p=0.007) kao i srednje jaka pozitivna korelacija s MELD stadijima (r=0.328, p=0.002).
U zaključku ADMA i NO usko su vezani uz promjene vezane za vaskularni endotel, te su njihove promjene pokazatelji vaskularne disfunkcije. Međutim još uvijek nedovoljno je razjašnjena njihova uloga i mehanizmi vezani uz vaskularnu disfunkciju u cirozi. Uznapredovalo oštećenje u cirozi jetre dovodi do akumulacije ADMA, narušavanjem njezinog normalnog metabolizma, Povišene razine ADMA-a mogu doprinijeti progresiji jetrene bolesti stoga regulacija metabolizma ADMA-e može predstavljati potencijalu terapijsku opciju liječenja vaskularne disfunkcije u cirozi, što otvara put mnogim budućim studijama. Less

Abstract (english)

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxid (NO) synthase, a molecule with proven vasodilatory effect, which makes it an important factor in pathophysiological processes of the vascular endothelium. Pathologic vascular phenomena that can be seen in liver cirrhosis, such as portal hypertension, hyperdynamic circulation, and hepatorenal syndrome, are thought to be caused by changes in ADMA plasma concetrations and their effect on NO synthesis.
The aim of... More this study was to define changes of ADMA plasma levels in patients with cirrhosis and the association of ADMA plasma levels with the severity of liver disease. This cross-sectional study included 90 adult patients with liver cirrhosis, of predominantly alcoholic etiology, with various severity of liver disease determined by the Child Pugh (CP) and MELD(Na) scores. Our results show ADMA levels for different groups of patients: CP-A=0,73 ug/l, CP-B=0,80 ug/l and CP-C=0,91 ug/l. In our study lower ADMA levels (0,73 ug/l) can be seen in patients with compensated liver disease (CP-A) and higher levels (0.87 ug/L) in patients with decompensated liver disease (CP-B+C), but there is no statistically significant difference between the groups (p=0,207). Our results also show a weak positive correlation between ADMA serum concetration and severity of disease based on the Child Pugh score (r=0.284, p=0.007) and a moderate positive correlation with severity of diseae based on the MELD score (r=0.328, p=0.002).
In conclusion, ADMA and NO are closely connected with changes of the vascular endhothelium, and they are also indicators of vascular dysfunction. However, their role remains unclear as well as mechanisms of vascular dysfunction in cirrhosis. Advanced liver injury in cirrhosis induces ADMA accumulation due to changes of metabolism. Increased ADMA levels cause progression of liver disease, therefore regulation of the ADMA metabolism could represent an option for treatment of vascular dysfunction in cirrhosis, which would clear the path for more upcoming studies. Less

• Keywords: asimetrčni dimetilarginin; dušikov oksid; ciroza jetre
• Keywords (english): asymmetric dimmethylarginine; nitric oxid; liver cirrhosis
• Language: croatian
• URN:NBN: urn:nbn:hr:105:139582
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-10-19 08:50:14