The assessment of qualitative and quantitative characteristics of high-density lipoproteins and their associations with markers of dyslipidemia metabolic syndrome

Metabolizam, struktura i funkcionalnost lipoproteina visoke gustine (high-density lipoproteins-HDL) su blisko povezani. Procenom kvalitatitvnih karakteristika HDL čestica se može dobiti detaljniji uvid u njihovu ateroprotektivnu aktivnost. U ovom istraživanju su ispitane karakteristike HDL čestica kod metaboličkog sindroma (MS) i pridruženih stanja koja predstavljaju faktore rizika za razvoj kardiovaskularnih bolesti (KVB). Uvid u remodelovanje HDL čestica je omogućen određivanjem relativne zastupljenosti pojedinačnih HDL subfrakcija, aktivnosti markera remodelovanja: lecitin-holesterol-acil transferaze (lecithin–cholesterol acyltransferase-LCAT) i holesterol-estar transfernog proteina (cholesteryl ester transfer protein-CETP), kao i koncentracije CETP. Antioksidativna funkcija HDL čestica je procenjena određivanjem paraoksonazne aktivnosti paraoksonaze 1 (PON1) i koncentracije PON1 i paraoksonaze 3 (PON3). Stepen oksidativne modifikacije antiaterogenih lipoproteinskih čestica je ispitan određivanjem koncentracije oksidovanog HDL (OxHDL). Dodatno su određene koncentracije serumskog amiloida A (SAA), leptina i adiponektina. Radi potvrde prisustva nealkoholne masne bolesti jetre (non-alcoholic fatty liver disease-NAFLD) je izračunat indeks masne jetre (fatty liver index-FLI). Dodatno. karakteristike HDL čestica su ispitane kod različitih metaboličkih fenotipova gojaznih i ispitanika sa prekomernom telesnom masom. Kod ispitanika sa MS su utvrđeni: dominacija manjih HDL subfrakcija, povišena aktivnost LCAT i koncentracija CETP. U grupi ispitanika sa MS su takođe uočeni povišena koncentracija OxHDL i vrednosti odnosa OxHDL/HDL-holesterol. Analizom karakteristika HDL čestica u odnosu na prisustvo pojedinačnih komponenti MS je utvrđeno remodelovanje u korist povećane zastupljenosti malih HDL subfrakcija u kategorijama ispitanika sa sniženom koncentracijom HDLholesterola, hipertrigliceridemijom i povećanim obimom struka. Snižena koncentracija PON3 je uočena kod ispitanika sa sniženom koncentracijom HDL-holesterola i povećanim obimom struka. Povišene vrednosti odnosa OxHDL/HDL-holesterol su utvrđene u kategorijama ispitanika sa sniženom koncentracijom HDL-holesterola, hipertrigliceridemijom i povišenom glukozom našte. Aktivnost LCAT je bila značajan prediktor povišenih vrednosti FLI. Odnos OxHDL/HDL-holesterol je bio značajan prediktor metabolički nezdravog fenotipa u kategorijama gojaznih i ispitanika sa prekomernom telesnom masom. Korelacionom analizom u celoj grupi ispitanika je utvrđeno da je odnos leptin/adiponektin je bio u pozitivnoj korelaciji sa relativnom zastupljenošću malih HDL čestica i negativno sa koncentracijom PON3. Aktivnost LCAT je pozitivno korelirala sa koncentracijom triglicerida, relativnom zastupljenošću malih HDL čestica i odnosom leptin/adiponektin. U ovom istraživanju su utvrđene izmenjene kvalitativne karakteristike HDL čestica kod MS i pridruženih stanja. Dominacija manjih HDL subfrakcija i povišen stepen oksidativne modifikacije HDL čestica su pokazatelji izmenjenih kvalitativnih odlika HDL čestica u uslovima višestrukih metaboličkih fakora rizika za KVB koji su prisutni kod MS. Dokazana je pozitivna veza između aktivnosti LCAT, kao markera remodelovanja HDL čestica, sa faktorima rizika za KVB: prisustvom MS i visokim vrednostima FLI, kao surogat markerom NAFLD. Izmenjene strukturne karakteristike HDL čestica, izražene kroz povišen stepen oksidativne modifikacije, mogu biti dodatni pokazatelj narušenog metaboličkog zdravlja gojaznih i ispitanika sa prekomernom telesnom masom. Sve ovo pokazuje da promenjene kvalitativne osobine antiaterogenih lipoproteina kod MS i srodnih stanja mogu biti dodatni element dislipidemije i faktor rizika za razvoj kardiometaboličkih komplikacija.High-density lipoproteins (HDL) metabolism, structure, and functionality are interrelated. Evaluation of HDL qualitative characteristics could give a more detailed insight into its atheroprotective activity. In this study, we evaluated HDL characteristics in subjects with metabolic syndrome (MS) and related conditions associated with higher risk for cardiovascular diseases (CVD). HDL particles remodeling was evaluated by estimating the relative proportion of each HDL subfraction, the activity of remodeling markers: lecithin–cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP), and CETP concentration. HDL antioxidative function was assessed through the determination of paraoxonase activity of paraoxonase 1 (PON1), as well as PON1 and paraoxonase 3 (PON3) concentrations. Oxidative modification of HDL particles was estimated as oxidatively modified HDL (OxHDL) concentration. Additionally, the concentrations of serum amyloid A (SAA), leptin and adiponectin were measured. Fatty liver index (FLI) was used as a surrogate marker for the presence of non-alcoholic fatty liver disease (NAFLD). In addition, HDL characteristics were evaluated in different metabolic phenotypes in the categories of overweight and obese subjects. Domination of smaller HDL subfractions, elevated LCAT activity, and CETP concentration, as well as increased OxHDL concentration and OxHDL/HDL-cholesterol ratio, were observed in subjects with MS. The analysis of HDL characteristics in the presence of individual MS components revealed remodeling in favor of smaller HDL subfractions in subjects with low HDL-cholesterol, hypertriglyceridemia, and elevated waist circumference. We found lower PON3 concentration in subjects with low HDL-cholesterol and elevated waist circumference. Increased OxHDL/HDLcholesterol ratio was found in subjects with low HDL-cholesterol, hypertriglyceridemia, and elevated fasting glucose. LCAT activity was positively associated with FLI. OxHDL/HDL-cholesterol ratio was a significant predictor of the metabolically unhealthy phenotype in overweight and obese subjects. In the entire group of subjects, leptin/adiponectin ratio correlated positively with the relative proportion of small HDL particles, and negatively with PON3 concentration. LCAT activity correlated positively with triglyceride concentration, relative proportion of small HDL particles, and leptin/adiponectin ratio. In this study, altered qualitative HDL characteristics in subjects with MS and related conditions were observed. Domination of smaller HDL subfractions and increased degree of HDL oxidative modification in subjects with MS indicate impaired HDL qualitative characteristics in the presence of multiple metabolic CVD risk factors associated with the presence of MS. LCAT activity was positively associated with the CVD risk factors: the presence of MS and elevated FLI values i.e. the presence of NAFLD. Altered HDL structural features, observed as an increased degree of HDL oxidative modification, can be an additional indicator of the metabolically unhealthy phenotype of overweight and obese subjects. Altered qualitative characteristics of antiatherogenic lipoproteins may represent additional components of dyslipidemia and cardiometabolic diseases risk factor in MS and related conditions