Značaj određivanja markera sinteza i apsorpcije holesterola kod zdravih ispitanika i pacijenata sa ishemijskom bolešću srca
The importance of cholesterol synthesis and absorption markers determination in healthy subjects and patients with ischemic heart disease.
Author
Gojković, TamaraMentor
Jelić-Ivanović, ZoranaCommittee members
Šobajić, SlađanaKalimanovska-Oštrić, Dimitra
Zeljković, Aleksandra
Vekić, Jelena
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Show full item recordAbstract
Ateroskleroza 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 ho...lesterola. 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...
Atherosclerosis 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 represe...nts 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...