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The importance of cholesterol synthesis and absorption markers determination in healthy subjects and patients with ischemic heart disease.

dc.contributor.advisorJelić-Ivanović, Zorana
dc.contributor.otherŠobajić, Slađana
dc.contributor.otherKalimanovska-Oštrić, Dimitra
dc.contributor.otherZeljković, Aleksandra
dc.contributor.otherVekić, Jelena
dc.creatorGojković, Tamara
dc.date.accessioned2019-07-18T13:25:23Z
dc.date.available2019-07-18T13:25:23Z
dc.date.available2020-07-03T09:48:20Z
dc.date.issued2018-12-25
dc.identifier.urihttp://eteze.bg.ac.rs/application/showtheses?thesesId=6820
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/11251
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:19912/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=2048345698
dc.description.abstractAteroskleroza predstavlja hroničnu, fokalnu bolest intime krvnih sudova. Iako je veliki broj etioloških faktora uključen u patogenezu i progresiju ateroskleroze, dislipidemija ima ključnu ulogu u razvoju ateroma. Ateroskleroza se nalazi u osnovi većine kardiovaskularnih bolesti (KVB), uključujući i ishemijsku bolest srca (IBS). Statini predstavljaju hipolipemike izbora u primarnoj i sekundarnoj prevenciji KVB. Pored dejstva na inhibiciju sinteze holesterola, statini ostvaruju i brojne plejotropne efekte. U rutinskoj praksi za postavljanje dijagnoze dislipidemije i praćenje odgovora na terapiju statinima koriste se osnovni parametri lipidnog statusa. Međutim, za sagledavanje celokupnog metabolizma holesterola i praćenje njegove homeostaze, neophodno je odrediti efikasnost sinteze i apsorpcije holesterola, njegovu raspodelu između lipoproteinskih čestica, kao i očuvanost funkcije reverznog transporta holesterola. Homeostaza holesterola predstavlja ravnotežu između sinteze i apsorpcije holesterola. Određivanje koncentracija prekursora u sintezi holesterola (dezmosterol i latosterol) i fitosterola (kampesterol, stigmasterol i β- sitosterol) kao surogat-markera apsorpcije holesterola, može ukazati na rani razvoj dislipidemije i predvideti odgovor na terapiju statinima. Jednim imenom ovi markeri se nazivaju neholesterolski steroli (NHS). Relativno niske koncentracije NHS predstavljaju specifičan problem za njihovu kvantifikaciju. Ovo je dodatni razlog za opsežnu validaciju metoda za određivanje NHS, kao i za utvrđivanjem preanalitičkih i analitičkih faktora uticaja na kvantifikaciju NHS. Kako bi se doprinelo boljem razumevanju metabolizma holesterola i uticaja terapije statinima na homeostazu holesterola, ciljevi ove studije su bili: uspostavljanje i validacija metode za određivanje NHS; određivanje koncentracija NHS kod zdravih ispitanika (KG) i pacijenata sa IBS; određivanje obrazaca homeostaze holesterola i njihove povezanosti sa osnovnim parametrima lipidnog statusa i raspodelom lipoproteinskih čestica male gustine (LDL) u ispitivanim grupama, i određivanje masene koncentracije fosfolipaze A2 udružene sa lipoproteinom (Lp-PLA2). U istraživanju je učestvovala 31 zdrava osoba, 32 pacijenta sa IBS na terapiji statinima i 47 pacijenata sa IBS bez terapije hipolipemicima. Koncentracije NHS i procentualni udeli pojedinačnih masnih kiselina (MK) u odnosu na ukupan masnokiselinski sastav plazme određivani su metodom gasne hromatografije sa plamenojonizacionom detekcijom (GC-FID). Relativni udeli pojedinih subklasa lipoproteina određeni su gradijent-gel elektroforezom. Masene koncentracije Lp-PLA2 određene su ELISA imunohemijskom metodom...sr
dc.description.abstractAtherosclerosis is a chronic, focal disease of the blood vessel intima. Even though many etiological factors are involved in the pathogenesis and progression of atherosclerosis, dyslipidemia has the key role in atheroma development. Atherosclerosis is the underlying cause of the most cardiovascular diseases (CVD), including coronary artery disease (CAD). Statins represent a hypolipemics of choice in primary and secondary CAD prevention. In addition to the inhibitory effect on cholesterol synthesis, statins also have numerous pleiotropic effects. Basic lipid parameters are used for diagnosing dyslipidemia and monitoring the statin therapy response in clinical practice. However, in order to examine the overall cholesterol metabolism and monitor its homeostasis, it is necessary to examine the efficiency of cholesterol synthesis and absorption, its distribution between lipoprotein particles, and the preservation of the reverse cholesterol transport function. Cholesterol homeostasis represents the balance between cholesterol synthesis and absorption. Non-cholesterol sterols (NCSs) represent cholesterol synthesis precursors (desmosterol and lathosterol) and cholesterol absorption surrogate markers (phytosterols - campesterol, stigmasterol and β-sitosterol). These markers can indicate early development of dyslipidemia and predict response to statin therapy. Relatively low NCSs concentrations represent a specific problem for their quantification. This represents the additional reason to conduct an extensive method validation for NCSs determination, as well as to resolve pre-analytical and analytical factors of influence. In order to contribute to a better understanding of cholesterol metabolism and the statin effects on cholesterol homeostasis, the objectives of this study were: establishing and validating the method for NHSs determination; determination of NHSs concentrations in healthy subjects (CG) and CAD patients; determination of cholesterol homeostasis patterns and their association with basic lipid parameters and distribution of low-density lipoprotein subclasses (LDL) in examined groups, and dtermination of lipoprotein-associated phospholipase A2 concentration. The study included 31 healthy controls (CG), 32 statin-treated patients and 47 statin-naive CAD patients. The NCSs concentrations and fatty acid (FA) profiles were determined by gas chromatography-flame ionization detection (GC-FID). Lipoprotein subclasses were separated by gradient gel electrophoresis and lipoprotein-associated phospholipase A2 concentration has been determined by ELISA assay...en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Фармацеутски факултетsr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175035/RS//
dc.rightsopenAccessen
dc.sourceУниверзитет у Београдуsr
dc.subjectdislipidemijasr
dc.subjectdyslipidemiaen
dc.subjectneholesterolski sterolisr
dc.subjecthomeostaza holesterolasr
dc.subjectvalidacija metode.sr
dc.subjectnon-cholesterol sterolsen
dc.subjectcholesterol homeostasisen
dc.subjectmethod validationen
dc.titleZnačaj određivanja markera sinteza i apsorpcije holesterola kod zdravih ispitanika i pacijenata sa ishemijskom bolešću srcasr
dc.title.alternativeThe importance of cholesterol synthesis and absorption markers determination in healthy subjects and patients with ischemic heart disease.en
dc.typedoctoralThesis
dc.rights.licenseBY-NC-ND
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/24482/IzvestajKomisije20674.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/24481/Disertacija.pdf


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