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

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-densitylipoproteins-HDL) su blisko povezani. Procenom kvalitatitvnih karakteristika HDL čestica se možedobiti detaljniji uvid u njihovu ateroprotektivnu aktivnost. U ovom istraživanju su ispitanekarakteristike HDL čestica kod metaboličkog sindroma (MS) i pridruženih stanja koja predstavljajufaktore rizika za razvoj kardiovaskularnih bolesti (KVB). Uvid u remodelovanje HDL čestica jeomogućen određivanjem relativne zastupljenosti pojedinačnih HDL subfrakcija, aktivnosti markeraremodelovanja: lecitin-holesterol-acil transferaze (lecithin–cholesterol acyltransferase-LCAT) iholesterol-estar transfernog proteina (cholesteryl ester transfer protein-CETP), kao i koncentracijeCETP. Antioksidativna funkcija HDL čestica je procenjena određivanjem paraoksonazne aktivnostiparaoksonaze 1 (PON1) i koncentracije PON1 i paraoksonaze 3 (PON3). Stepen oksidativnemodifikacije antiaterogenih lipoproteinskih čestica je ispitan određivanjem koncentracijeoksidovanog HDL (OxHDL). Dodatno su određene koncentracije serumskog amiloida A (SAA),leptina i adiponektina. Radi potvrde prisustva nealkoholne masne bolesti jetre (non-alcoholic fattyliver disease-NAFLD) je izračunat indeks masne jetre (fatty liver index-FLI). Dodatno. karakteristikeHDL čestica su ispitane kod različitih metaboličkih fenotipova gojaznih i ispitanika sa prekomernomtelesnom masom.Kod ispitanika sa MS su utvrđeni: dominacija manjih HDL subfrakcija, povišena aktivnostLCAT i koncentracija CETP. U grupi ispitanika sa MS su takođe uočeni povišena koncentracijaOxHDL i vrednosti odnosa OxHDL/HDL-holesterol. Analizom karakteristika HDL čestica u odnosuna prisustvo pojedinačnih komponenti MS je utvrđeno remodelovanje u korist povećanezastupljenosti malih HDL subfrakcija u kategorijama ispitanika sa sniženom koncentracijom HDLholesterola,hipertrigliceridemijom i povećanim obimom struka. Snižena koncentracija PON3 jeuočena kod ispitanika sa sniženom koncentracijom HDL-holesterola i povećanim obimom struka.Povišene vrednosti odnosa OxHDL/HDL-holesterol su utvrđene u kategorijama ispitanika sasniženom koncentracijom HDL-holesterola, hipertrigliceridemijom i povišenom glukozom našte.Aktivnost LCAT je bila značajan prediktor povišenih vrednosti FLI. Odnos OxHDL/HDL-holesterolje bio značajan prediktor metabolički nezdravog fenotipa u kategorijama gojaznih i ispitanika saprekomernom telesnom masom. Korelacionom analizom u celoj grupi ispitanika je utvrđeno da jeodnos leptin/adiponektin je bio u pozitivnoj korelaciji sa relativnom zastupljenošću malih HDLčestica i negativno sa koncentracijom PON3. Aktivnost LCAT je pozitivno korelirala sakoncentracijom triglicerida, relativnom zastupljenošću malih HDL čestica i odnosomleptin/adiponektin.U ovom istraživanju su utvrđene izmenjene kvalitativne karakteristike HDL čestica kod MS ipridruženih stanja. Dominacija manjih HDL subfrakcija i povišen stepen oksidativne modifikacijeHDL čestica su pokazatelji izmenjenih kvalitativnih odlika HDL čestica u uslovima višestrukihmetaboličkih fakora rizika za KVB koji su prisutni kod MS. Dokazana je pozitivna veza izmeđuaktivnosti LCAT, kao markera remodelovanja HDL čestica, sa faktorima rizika za KVB: prisustvomMS i visokim vrednostima FLI, kao surogat markerom NAFLD. Izmenjene strukturne karakteristikeHDL čestica, izražene kroz povišen stepen oksidativne modifikacije, mogu biti dodatni pokazateljnarušenog metaboličkog zdravlja gojaznih i ispitanika sa prekomernom telesnom masom. Sve ovopokazuje da promenjene kvalitativne osobine antiaterogenih lipoproteina kod MS i srodnih stanjamogu 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 itsatheroprotective activity. In this study, we evaluated HDL characteristics in subjects with metabolicsyndrome (MS) and related conditions associated with higher risk for cardiovascular diseases (CVD).HDL particles remodeling was evaluated by estimating the relative proportion of each HDLsubfraction, the activity of remodeling markers: lecithin–cholesterol acyltransferase (LCAT) andcholesteryl ester transfer protein (CETP), and CETP concentration. HDL antioxidative function wasassessed through the determination of paraoxonase activity of paraoxonase 1 (PON1), as well asPON1 and paraoxonase 3 (PON3) concentrations. Oxidative modification of HDL particles wasestimated as oxidatively modified HDL (OxHDL) concentration. Additionally, the concentrations ofserum amyloid A (SAA), leptin and adiponectin were measured. Fatty liver index (FLI) was used asa surrogate marker for the presence of non-alcoholic fatty liver disease (NAFLD). In addition, HDLcharacteristics were evaluated in different metabolic phenotypes in the categories of overweight andobese 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 insubjects with MS. The analysis of HDL characteristics in the presence of individual MS componentsrevealed remodeling in favor of smaller HDL subfractions in subjects with low HDL-cholesterol,hypertriglyceridemia, and elevated waist circumference. We found lower PON3 concentration insubjects with low HDL-cholesterol and elevated waist circumference. Increased OxHDL/HDLcholesterolratio was found in subjects with low HDL-cholesterol, hypertriglyceridemia, and elevatedfasting glucose. LCAT activity was positively associated with FLI. OxHDL/HDL-cholesterol ratiowas a significant predictor of the metabolically unhealthy phenotype in overweight and obesesubjects. In the entire group of subjects, leptin/adiponectin ratio correlated positively with the relativeproportion of small HDL particles, and negatively with PON3 concentration. LCAT activitycorrelated positively with triglyceride concentration, relative proportion of small HDL particles, andleptin/adiponectin ratio.In this study, altered qualitative HDL characteristics in subjects with MS and relatedconditions were observed. Domination of smaller HDL subfractions and increased degree of HDLoxidative modification in subjects with MS indicate impaired HDL qualitative characteristics in thepresence of multiple metabolic CVD risk factors associated with the presence of MS. LCAT activitywas 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 HDLoxidative modification, can be an additional indicator of the metabolically unhealthy phenotype ofoverweight and obese subjects. Altered qualitative characteristics of antiatherogenic lipoproteins mayrepresent additional components of dyslipidemia and cardiometabolic diseases risk factor in MS andrelated conditions

Efekat suplementacije propolisom i N-acetilcisteinom na raspodelu lipoproteinskih supklasa i aktivnosti paraoksonaze 1 u osoba sa akutnom respiratornom infekcijom

Background:Propolis and N-acetylcysteine have positiveimpact on respiratory tract health. Also, it has been sug-gested that they have beneficial effects on serum lipid andoxidative stress status, but the available data are limitedand mostly gained from animal models. In this study weevaluated the effects of propolis and N-acetylcysteine sup-plementation (PropoMucil®) on lipid status, lipoproteinsubclasses distribution and paraoxonase 1 activity in sub-jects with acute respiratory infection.Methods:Twenty subjects with acute respiratory infectionwere included. PropoMucil®granules for oral solution (80mg of dry propolis extract and 200 mg of N-acetylcysteine)were administered tree times per day for ten days. Serumlipid profile, paraoxonase 1 activity and low-density andhigh-density lipoprotein size and subclasses distributionwere assessed at baseline and after supplementation.Results:Following ten days of supplementation lipid statusremained unchanged, but a significant increase of low-density lipoprotein particle size and proportion of high-den-sity lipoprotein 3a particles were found (P<0.05).Moreover, supplementation with PropoMucil®significantlyimproved high-density lipoprotein particles distribution, particularly in those who smoke. There was a moderateincrease of paraoxonase 1 activity, but without statisticalsignificance.Conclusions:The presented study demonstrated that short-term supplementation with PropoMucil®has beneficialeffects on low-density and high-density lipoprotein sub-classes distribution and paraoxonase 1 activity in subjectswith acute respiratory infection particularly in those whosmoke.Uvod: Propolis i N-acetilcistein pozitivno utiču na zdravlje disajnih puteva. Takođe, sugeriše se da oni imaju blagotvorno dejstvo na lipidni i oksidativno-stresni status, ali podaci su ograničeni i dobijeni uglavnom na životinjskim modelima. U ovom istraživanju, procenili smo kombinovani efekat propolisa i N-acetilcisteina (PropoMucil®) na status lipida, raspodelu supklasa lipoproteina i aktivnost paraoksonaze 1 kod pacijenata sa akutnom respiratornom infekcijom (ARI). Metode: Uključeno je 20 ispitanika sa akutnom respiratornom infekcijom. Oralni rastvor praška PropoMucil® (80 mg suvog ekstrakta propolisa i 200 mg N-acetilcisteina) je aplikovan 3 puta dnevno tokom 10 dana. Serumski lipidni profil, aktivnost praoksonaze 1 i veličina i raspodela supfrakcija lipoproteina niske gustine i lipoproteina visoke gustine su određeni pre i nakon suplementacije. Rezultati: Nakon deset dana suplementacije, lipidni status je ostao nepromenjen, ali je utvrđeno značajno povećanje veličine lipoproteina niske gustine i relativnog udela lipoproteina visoke gustine 3a (P <0,05). Pored toga, suplementacija PropoMucil®-om značajno je poboljšala distribuciju lipoproteinskih čestica visoke gustine, posebno kod pacijenata koji puše. Došlo je do umerenog porasta aktivnosti paraoksonaze 1, ali bez statističke značajnosti. Zaključak: Studija je pokazala da kratkotrajna suplementacija PropoMucil®-om ima korisne efekte na distribuciju supklasa lipoproteina niske i visoke gustine i aktivnost paraoksonaze 1 kod ispitanika sa akutnom respiratornom infekcijom, posebno kod onih koji puše

Significance of LDL and HDL subclasses characterization in the assessment of risk for colorectal cancer development

Introduction: Dyslipidaemia contributes to the occurrence of colorectal cancer (CRC). We hypothesized that qualitative changes of lipoproteins are associated with the risk for CRC development. This study analyses low-density lipoprotein (LDL) and high-density lipoprotein (HDL) diameters, as well as distribution of LDL and HDL subclasses in patients with CRC, with an aim to determine whether advanced lipid testing might be useful in predicting the risk for the onset of this malignancy. Materials and methods: This case-control study included 84 patients with newly diagnosed CRC and 92 controls. Gradient gel electrophoresis was applied for separation of lipoprotein subclasses and for LDL and HDL diameters determination. Lipid parameters were measured using routine enzymatic methods. Results: Total cholesterol, HDL and LDL-cholesterol were significantly lower in CRC patients compared to controls (4.47 mmol/L vs. 5.63 mmol/L; 0.99 mmol/L vs. 1.27 mmol/L; 2.90 mmol/L vs. 3.66 mmol/L; P lt 0.001, respectively). Patients had significantly smaller LDL (25.14 nm vs. 26.92 nm; P lt 0.001) and HDL diameters (8.76 nm vs. 10.17 nm; P lt 0.001) and greater proportion of small, dense LDL particles (54.0% vs. 52.9%; P = 0.044) than controls. Decreased LDL and HDL diameters were independent predictors of CRC (OR = 0.5, P = 0.001 and OR = 0.5, P = 0.008, respectively), and alongside with age and HDL-cholesterol concentrations formed the optimal cost-effective model, providing adequate discriminative abilities for CRC (AUC = 0.89) and correct patients classification (81%). Conclusions: Patients with CRC have decreased LDL and HDL diameters and increased proportion of smaller particles. LDL and HDL diameters determination could be useful in assessing the risk for CRC development

Association between proprotein convertase subtilisin/kexin 9 (PCSK9) and lipoprotein subclasses in children with type 1 diabetes mellitus: Effects of glycemic control

Background and aims: Dyslipidemia in type 1 diabetes mellitus (T1DM) is characterised by altered distributions of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses. Recent studies suggested that proprotein convertase subtilisin/kexin 9 (PCSK9) may contribute to the development of dyslipidemia in T1DM. In this cross-sectional study, we investigated the association between PCSK9 and lipoprotein subclasses in young T1DM patients, with respect to glycemic control. Methods: Plasma PCSK9 and lipoprotein subclasses were determined in 207 patients with T1DM (106 boys and 101 girls), aged 13.9 +/- 3.0 years and treated by intensive insulin therapy. Results: Plasma PCSK9 levels significantly increased with worsening of glycemic control (p lt 0.001). T1DM patients with poor glucoregulation had the highest proportion of small, dense LDL (sdLDL) and smaller HDL particles, as well. PCSK9 was positively associated with markers of glucose homeostasis and serum lipid parameters only in patients with suboptimal/poor glucoregulation. In well-controlled T1DM, plasma PCSK9 level was inversely associated with a relative proportion of sdLDL particles (p lt 0.01) and this association remained significant in multivariate analysis. In T1DM patients with suboptimal/poor glycemic control, PCSK9 was positively associated with the proportion of the smallest HDL3c particles (p lt 0.001), but negatively with HDL size (p lt 0.05). Conclusions: The extent of achieved metabolic control modifies the association between PCSK9 and lipoprotein subclasses in T1DM. Further investigations are needed to reveal whether the observed effects of glycemic control on PCSK9 and sdLDL levels have causal consequences on CVD risk in young patients with T1DM

Associations of Apgar score and size at birth with lipoprotein subclasses in juvenile obesity

N Background/aim: Juvenile obesity is associated with several metabolic abnormalities, one of them being atherogenic dyslipidemia. Suboptimal fetal growth is associated with obesity risk in childhood, but also with increased rate of metabolic diseases in later life. This study investigated associations of neonatal data (Apgar score, birth weight and birth length) with low-density lipoprotein and high-density lipoprotein (LDL and HDL) subclasses in a group of obese children, as well as a possible impact of breastfeeding duration on obesity-associated lipoprotein subclasses distributions. Materials and methods: We included 42 obese children, aged 14.2 +/- 2.1 years. LDL and HDL subfractions were separated by gradient gel electrophoresis and biochemical parameters were assessed by routine methods. Results: Compared with obese children with Apgar >= 9, the group with Apgar lt 9 had significantly higher percentages of small, dense LDL particles (P lt 0.05), due to reduced LDL I (P lt 0.01) and increased LDL III subclasses (P lt 0.05). Birth weight was positively associated with the proportions of LDL I particles (P lt 0.001), whereas birth height positively correlated with the amount of HDL 2b subclasses (P lt 0.05). The group of never or less than 3 months breastfed children had significantly smaller LDL size (P lt 0.01) and lower proportion of HDL 2a particles (P lt 0.05) than their >= 3 months breastfed peers. Conclusion: The results showed significant associations of neonatal characteristics with LDL and HDL particle distributions in obese children. In addition, our results point toward positive aspects of longer breastfeeding duration on lipoprotein particle distributions in obese children

Association of acute Babesia canis infection and serum lipid, lipoprotein, and apoprotein concentrations in dogs

Background: Babesia canis infection induces a marked acute phase response (APR) that might be associated with alteration in lipid and lipoprotein metabolism and disease prognosis. Hypothesis: Dogs with B. canis-induced APR develop dyslipidemia with altered lipoprotein concentration and morphology. Animals: Twenty-nine client-owned dogs with acute B. canis infection and 10 clinically healthy control dogs. Methods: Observational cross-sectional study. Serum amyloid A (SAA) was measured using ELISA. Cholesterol, phospholipids, and triglycerides were determined biochemically. Lipoproteins were separated using agarose gel electrophoresis. Lipoprotein diameter was assessed by polyacrylamide gradient gel electrophoresis; correlation with ApoA-1 (radioimmunoassay) and SAA was determined. Results: Dogs with B. canis infection had a marked APR (median SAA, 168.3 μg/mL; range, 98.1-716.2 μg/mL) compared with controls (3.2 μg/mL, 2.0-4.2 μg/mL) (P lt .001). Dogs with B. canis infection had significantly lower median cholesterol (4.79 mmol/L, 1.89-7.64 mmol/L versus 6.15 mmol/L, 4.2-7.4 mmol/L) (P =.02), phospholipid (4.64 mmol/L, 2.6-6.6 mmol/L versus 5.72 mmol/L, 4.68-7.0 mmol/L) (P =.02), and α-lipoproteins (77.5%, 27.7%-93.5% versus 89.2%, 75.1%-93.5%) (P =.04), and higher ApoA-1 (1.36 U, 0.8-2.56 U versus 0.95 U, 0.73-1.54 U) concentrations (P =.02). Serum amyloid A correlated with high-density lipoproteins (HDLs) diameter (rho =.43; P =.03) and ApoA-1 (rho =.63, P lt .001). Conclusions and Clinical Importance: Major changes associated with B. canis-induced APR in dogs are related to concentration, composition, and morphology of HDL particles pointing to an altered reverse cholesterol transport. Parallel ApoA-1 and SAA concentration increase is a unique still unexplained pathophysiological finding

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

The association between lecithin–cholesterol acyltransferase activity and fatty liver index

Background: Non-alcoholic fatty liver disease is a frequent ailment with known complications, including those within the cardiovascular system. Associations between several indicators of high-density lipoprotein metabolism and function with clinical and laboratory parameters for the assessment of fatty liver index, a surrogate marker of non-alcoholic fatty liver disease, were evaluated. Methods: The study comprised 130 patients classified according to fatty liver index values: fatty liver index lt 30, fatty liver index 30–59 (the intermediate group) and fatty liver index ⩾ 60. Lecithin–cholesterol acyltransferase and cholesteryl ester transfer protein activities were determined. Paraoxonase 1 concentration and its activity, paraoxonase 3 concentration and high-density lipoprotein subclass distribution were assessed. Results: Increased lecithin–cholesterol acyltransferase activity correlated with increased fatty liver index (P lt 0.001). Paraoxonase 3 concentration was lower in the fatty liver index ⩾ 60 group compared with the fatty liver index lt 30 group (P lt 0.05). Cholesteryl ester transfer protein activity, paraoxonase 1 concentration and its activity did not significantly differ across the fatty liver index groups. The relative proportion of small-sized high-density lipoprotein 3 subclass was higher in the fatty liver index ⩾ 60 group compared with the other two fatty liver index groups (P lt 0.01). Lecithin–cholesterol acyltransferase activity positively associated with the fatty liver index ⩾ 60 group and remained significant after adjustment for other potential confounders. Only the triglyceride concentration remained significantly associated with lecithin–cholesterol acyltransferase activity when the parameters that constitute the fatty liver index equation were examined. Conclusions: Higher lecithin–cholesterol acyltransferase activity is associated with elevated fatty liver index values. Significant independent association between triglycerides and lecithin–cholesterol acyltransferase activity might indicate a role of hypertriglyceridaemia in alterations of lecithin–cholesterol acyltransferase activity in individuals with elevated fatty liver index

Oxidative stress and paraoxonase 1 status in acute ischemic stroke patients

Objective: The connection of oxidative stress with dyslipidemia creates a newly-emerging atherosclerosis risk factor involved in acute ischemic stroke development. This study analyzed the influence of oxidative stress on structural changes of high-density lipoprotein (HDL) particles connected with modification in protective paraoxonase 1 (PON1) activity. Methods: This study used 185 patients with acute ischemic stroke and 185 apparently healthy controls. Oxidative stress status, PON1 status, lipids and high-sensitivity C-reactive protein (hsCRP) were determined. In isolated HDL lipoprotein fraction we determined selected markers of oxidative stress (malondialdehyde, MDA) and the content of total sulfhydryl (SH) groups. The capability of oxidative and PON1 status parameters to discriminate patients according to survival status was evaluated. Results: Stroke patients had lower HDL-cholesterol than controls and a remarkable fall in PON1 activity (control group-227 U/L, survivors-42 U/L, lethal outcome group-61 U/L, p lt 0.001), along with more prominent inflammation. Pronounced oxidative stress and impaired antioxidative protection was present among patients. HDL fraction analysis revealed a significant decrease of SH groups content (control group vs. patients, p lt 0.05) and increased in MDA content in patients (lethal outcome vs. control group, p lt 0.05). According to logistic regression analysis, the best predictor of disease outcome was oxidative stress marker - prooxidative-antioxidative balance (PAB). Conclusions: Pronounced oxidative stress in this group of acute ischemic stroke patients probably led to HDL structural changes, which could further cause an alteration or decrease of PON1 activity. Evidence of increased prooxidant level associated with decreased protective, antioxidative factors suggests their mutual involvement in this complex pathology