As a member of the apolipoprotein C (ApoC) family with a relatively high content, ApoC3 plays a major role in the regulation of triglyceride metabolism, and plays an important role in the occurrence and development of cardiovascular diseases, glucose and lipid metabolism disorders. Nonalcoholic fatty liver disease (NAFLD) refers to the accumulation of a large amount of fat in the liver in the absence of a history of chronic alcohol consumption or other damage to the liver. A large number of previous studies have shown that there is a correlation between the gene polymorphism and high expression of ApoC3 and NAFLD. In the context of hypertriglyceridemia (HTG), this article reviews the relationship between ApoC3 and NAFLD, glucose and lipid metabolism, and islet β cell function, showing that ApoC3 can not only inhibit lipoprotein lipase (LPL) and hepatic lipase (HL) activity, delay the decomposition of triglyceride in plasma to maintain the body's energy metabolism during fasting, but also be significantly increased under insulin resistance, prompting the liver to secrete a large amount of very low-density lipoprotein (VLDL) to induce HTG. Therefore, targeting and inhibiting ApoC3 might become a new approach to treat HTG. Increasing evidence suggests that ApoC3 does not appear to be an independent "contributor" to NAFLD. Similarly, our previous studies have shown that ApoC3 is not an independent factor triggering islet β cell dysfunction in ApoC3 transgenic mice, but in a state of excess nutrition, HTG triggered by ApoC3 high expression may exacerbate the effects of hyperglycemia and insulin resistance on islet β cell function, and the underlying mechanism remains to be further discussed.
Apolipoprotein C-III/genetics* ; Non-alcoholic Fatty Liver Disease/pathology* ; Glucose/metabolism* ; Lipid Metabolism ; Humans ; Animals ; Hypertriglyceridemia/metabolism* ; Islets of Langerhans/metabolism*

The present study observed the regulatory effect of total flavonoids of Ziziphora clinopodioides on autophagy and the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathways in ApoE~(-/-) mice and explored the mechanism of total flavonoids of Z. clinopodioides against atherosclerosis(AS). ApoE~(-/-) mice were fed on a high-fat diet for eight weeks to induce an AS model. The model mice were randomly divided into a model group, a positive control group, and low-, medium-and high-dose groups of total flavonoids of Z. clinopodioides, while C57BL/6J mice fed on a common diet were assigned to the blank group. The serum and aorta samples were collected after intragastric administration for 12 weeks, and the serum levels of total cholesterol(TC), triglyceride(TG), low density lipoprotein-cholesterol(LDL-C), and high density lipoprotein-cholesterol(HDL-C) were detected by an automatic biochemical analyzer. The serum expression levels of intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), matrix metalloproteinase-2(MMP-2), and matrix metalloprotei-nase-9(MMP-9) were detected by enzyme-linked immunosorbent assay(ELISA). Oil red O staining was used to observe the aortic plaque area in mice. Hematoxylin-eosin(HE) staining was used to observe the aortic plaque and pathological changes in mice. The expression of P62 and LC3 in the aorta was detected by the immunofluorescence method. The protein expression of LC3Ⅱ/Ⅰ, Beclin-1, P62, p-PI3K, p-Akt, and p-mTOR in the aorta of mice was detected by Western blot. The results showed that compared with the blank group, the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2 and MMP-9 in the model group were significantly increased(P<0.01 or P<0.05), the content of HDL-C was decreased(P<0.05), intra-aortic plaque area was enlarged(P<0.01), the expression of LC3 in the aorta was significantly down-regulated, P62 expression was up-regulated(P<0.01 or P<0.05), the expressions of LC3Ⅱ/Ⅰ and Beclin-1 in the aortic lysate were significantly down-regulated, and the expressions of p-PI3K, p-Akt, p-mTOR and P62 were significantly increased(P<0.01). The medium-and high-dose groups of total flavonoids of Z. clinopodioides could reduce the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2, and MMP-9 in AS model mice(P<0.01 or P<0.05), and increase the content of HDL-C(P<0.01 or P<0.05). The aortic plaque area of mice after middle and high doses of total flavonoids of Z. clinopodioides was significantly reduced(P<0.01), the content of foam cells decrease, and the narrowing of the lumen decreased. The total flavonoids of Z. clinopodioides significantly increased the expression of LC3 in the aorta and the expression of LC3Ⅱ/Ⅰ and Beclin-1 in the lysate, and decreased the expression of P62 in the aorta and the expression of p-PI3K, p-Akt, p-mTOR and P62 in the lysate(P<0.01 or P<0.05). The results showed that the total flavonoids of Z. clinopodioides could improve the content of blood lipids and inflammatory factors, and reduce the generation of foam cells and plaques in aortic tissue, and the mechanism may be related to the regulation of PI3K/Akt/mTOR signaling pathway.
Animals ; Mice ; Apolipoproteins E ; Atherosclerosis/genetics* ; Beclin-1 ; Cholesterol, LDL ; Intercellular Adhesion Molecule-1 ; Matrix Metalloproteinase 2/genetics* ; Matrix Metalloproteinase 9/genetics* ; Mice, Inbred C57BL ; Phosphatidylinositol 3-Kinases/metabolism* ; Plaque, Atherosclerotic ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/genetics* ; Vascular Cell Adhesion Molecule-1/genetics*

The hepatitis C virus (HCV) is a globally prevalent human pathogen that causes persistent liver infections in most infected individuals. Several studies reported that HCV particles are enriched in apolipoprotein E (apoE) and that apoE is required for HCV infectivity and production. However, the relationship between apoE gene polymorphisms and HCV genotypes in patients with HCV is less well understood. The aim of this study was to investigate the association between apoE gene polymorphism and HCV genotypes in patients. The HCV genotypes were identified among the 124 patients infected with HCV, and the genetic characteristics of the HCV genotype were analyzed. In addition, the results of the clinical laboratory test were comparatively analyzed according to the classified genotypes. Both HCV 1b (n=80) and 2a (n=42) patients had higher AFP, AST, ALT, ALP, γ-GTP, apoB, and apoE values compared with the normal control group. In particular, apoB and apoE levels were statistically significantly higher in the HCV 2a patients (P<0.05) and apoE levels were significantly higher in the HCV 1b patients (P<0.000). According to the results the patients with HCV genotype 1b showed higher values of liver damage related indicators and apoB expression than the patients with HCV genotype 2a. The fat related indicators and apoE expression were not different between the two major HCV genotypes (2a and 1b). We anticipate that the apoE ε3 allele is the most common type in HCV genotype 1b (89.2%) and 2a (91.7%). As a result of apoE genotyping, we confirmed an association with HCV infection and the apoE ε3 allele. However, the ratios of the apoE ε3 allele among the patients with genotype 1b and 2a were similar to each other.
Alleles ; Apolipoproteins B ; Apolipoproteins E ; Apolipoproteins ; Genotype ; Hepacivirus ; Hepatitis C ; Hepatitis ; Humans ; Liver

Serum cholesterol is major risk factor and contributor to atherosclerotic cardiovascular disease (ASCVD). Therapeutic cholesterol-lowering drugs, especially statin, revealed that reduction in low-density lipoprotein cholesterol (LDL-C) produces marked reduction of ASCVD events. In the preventive scope, lower LDL-C is generally accepted as better in proven ASCVD patients and high-risk patient groups. However, in patients with low to intermediate risk without ASCVD, risk assessment is clinically guided by traditional major risk factors. In this group, the complement approach to detailed risk assessment about traditional major risk factors is needed. These non-traditional risk factors include ankle-brachial index (ABI), high-sensitivity C-reactive protein (hsCRP) level, lipoprotein(a) (Lp[a]), apolipoprotein B (apoB), or coronary artery calcium (CAC) score. CAC measurements have an additive role in the decision to use statin therapy in non-diabetic patients 40–75 years old with intermediate risk in primary prevention. This review comprises ASCVD lipid/biomarkers other than CAC. The 2013 and 2018 American College of Cardiology/American Heart Association (ACC/AHA) guidelines suggest these factors as risk-enhancing factors to help health care providers better determine individualized risk and treatment options especially regarding abnormal biomarkers. The recent 2018 Korean guidelines for management of dyslipidemia did not include these biomarkers in clinical decision making. The current review describes the current roles of hsCRP, ABI, LP(a), and apoB in personal modulation and management of health based on the 2018 ACC/AHA guideline on the management of blood cholesterol.
Ankle Brachial Index ; Apolipoproteins ; Apolipoproteins B ; Biomarkers ; C-Reactive Protein ; Calcium ; Cardiovascular Diseases ; Cholesterol ; Clinical Decision-Making ; Complement System Proteins ; Coronary Vessels ; Dyslipidemias ; Health Personnel ; Heart ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Lipoprotein(a) ; Lipoproteins ; Primary Prevention ; Risk Assessment ; Risk Factors

Although elevated serum low-density lipoprotein-cholesterol (LDL-C) is without any doubts accepted as an important risk factor for cardiovascular disease (CVD), the role of elevated triglycerides (TGs)-rich lipoproteins as an independent risk factor has until recently been quite controversial. Recent data strongly suggest that elevated TG-rich lipoproteins are an independent risk factor for CVD and that therapeutic targeting of them could possibly provide further benefit in reducing CVD morbidity, events and mortality, apart from LDL-C lowering. Today elevated TGs are treated with lifestyle interventions, and with fibrates which could be combined with omega-3 fatty acids. There are also some new drugs. Volanesorsen, is an antisense oligonucleotid that inhibits the production of the Apo C-III which is crucial in regulating TGs metabolism because it inhibits lipoprotein lipase (LPL) and hepatic lipase activity but also hepatic uptake of TGs-rich particles. Evinacumab is a monoclonal antibody against angiopoietin-like protein 3 (ANGPTL3) and it seems that it can substantially lower elevated TGs levels because ANGPTL3 also regulates TGs metabolism. Pemafibrate is a selective peroxisome proliferator-activated receptor alpha modulator which also decreases TGs, and improves other lipid parameters. It seems that it also has some other possible antiatherogenic effects. Alipogene tiparvovec is a nonreplicating adeno-associated viral vector that delivers copies of the LPL gene to muscle tissue which accelerates the clearance of TG-rich lipoproteins thus decreasing extremely high TGs levels. Pradigastat is a novel diacylglycerol acyltransferase 1 inhibitor which substantially reduces extremely high TGs levels and appears to be promising in treatment of the rare familial chylomicronemia syndrome.
Apolipoprotein C-III ; Cardiovascular Diseases ; Diacylglycerol O-Acyltransferase ; Fatty Acids, Omega-3 ; Fibric Acids ; Hyperlipoproteinemia Type I ; Life Style ; Lipase ; Lipoprotein Lipase ; Lipoproteins ; Metabolism ; Mortality ; PPAR alpha ; Risk Factors ; Triglycerides

Serum levels of the pro-inflammatory apolipoprotein CIII (apoCIII) are increased in type-1 diabetic (T1D) patients and when β-cells are exposed to apoCIII they undergo apoptosis, which can be prevented by an antibody against apoCIII. We have previously investigated the BB rat, an animal model that develops a human-like T1D at the age of around 60 days, and found that apoCIII was also increased in sera from pre-diabetic rats and this promoted β-cell death. Lowering apoCIII with an oligonucleotide antisense during a phase of the pre-diabetic period prolonged the time to onset of T1D. In order to find other ways to lower apoCIII we in this study tested non-alcoholic red wine with medium and high concentrations of polyphenols and the lipid-lowering drug, fenofibrate, both reported to decrease the expression of apoCIII by activating peroxisome proliferator-activated receptors. Pre-diabetic BB-rats were treated orally for one month prior to the expected onset of diabetes with the two different wines or fenofibrate. None of the treatments prevented or prolonged the time to onset of diabetes and the expression of apoCIII was unaffected in this animal model for T1D. However, it must be emphasized that this does not exclude that other species can show a response to these substances.
Animals ; Apolipoprotein C-III ; Apoptosis ; Diabetes Mellitus* ; Fenofibrate* ; Humans ; Models, Animal ; Peroxisome Proliferator-Activated Receptors ; Polyphenols ; Rats ; Rats, Inbred BB* ; Wine*

BACKGROUND/AIMS: Changes in lipid profiles in patients infected with hepatitis C virus (HCV) during direct-acting antiviral therapy have been reported in recent years. However, the clinical aspects of disturbed lipid metabolism in chronic HCV infection have not been fully elucidated. METHODS: Dynamic changes in serum total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol and apolipoprotein levels in patients infected with HCV genotype 1b were examined during combination therapy with daclatasvir (DCV) and asunaprevir (ASV). RESULTS: Total, LDL−, and HDL-cholesterol levels increased rapidly and persistently after week 4. Apolipoprotein (apo) A-I, apo B, apo C-II, and apo C-III levels were significantly higher at week 4 than at week 0. In contrast, apo A-II and apo E levels were significantly lower. The differences in LDL− and HDL-cholesterol levels were positively correlated with those of apo B and apo A-I, respectively. Interestingly, in patients with non-sustained virological response, these cholesterol levels decreased rapidly after viral breakthrough or viral relapse. Furthermore, similar changes were observed for apo A-I, apo B and apo C-III levels. CONCLUSIONS: Clearance of HCV using combination therapy with DCV and ASV results in rapid changes in serum lipid profiles, suggesting an influence of HCV infection on disturbed lipid metabolism.
Apolipoprotein A-I ; Apolipoprotein A-II ; Apolipoprotein C-II ; Apolipoprotein C-III ; Apolipoproteins ; Apolipoproteins B ; Apolipoproteins E ; Cholesterol ; Genotype ; Hepacivirus* ; Hepatitis C* ; Hepatitis* ; Humans ; Lipid Metabolism ; Lipoproteins ; Recurrence

OBJECTIVEAssessment of the comprehensive relationship among apolipoprotein CIII (apoCIII) levels, inflammation, and metabolic disorders is rare.

METHODSA total of 1455 consecutive patients not treated with lipid-lowering drugs and undergoing coronary angiography were enrolled in this cross-sectional study. A mediation analysis was used to detect the underlying role of apoCIII in the association of inflammation with metabolic syndrome (MetS).

RESULTSPatients with MetS showed higher levels of apoCIII [95.1 (73.1-131.4) vs. 81.7 (58.6-112.4) μg/mL, P < 0.001] and inflammatory markers [high sensitivity C-reactive protein, 1.7 (0.8-3.4) vs. 1.1 (0.5-2.2) mg/L; white blood cell count, (6.48 ± 1.68) vs. (6.11 ± 1.67) × 109/L]. The levels of apoCIII and inflammatory markers increased with the number of metabolic risk components (all P < 0.001). Furthermore, apoCIII levels were associated with virtually all individual MetS risk factors and inflammatory markers (all P < 0.05). Importantly, the prevalence of MetS in each metabolic disorder rose as apoCIII levels increased (all P < 0.05). Mediation analysis showed that apoCIII partially mediated the effect of inflammation on MetS independently from triglycerides.

CONCLUSIONPlasma apoCIII levels were significantly associated with the development and severity of MetS, and a role of apoCIII in the effect of inflammation on the development of MetS was identified.

Adult ; Aged ; Apolipoprotein C-III ; blood ; Biomarkers ; blood ; C-Reactive Protein ; metabolism ; Coronary Angiography ; Cross-Sectional Studies ; Female ; Humans ; Inflammation ; blood ; Leukocyte Count ; Male ; Metabolic Syndrome ; blood ; Middle Aged

Hepatitis B virus (HBV) and hepatitis C virus (HCV) chronically cause hepatitis, liver cirrhosis, and hepatocellular carcinoma, and biomarkers related to liver damage are elevated in HBV and HCV patients. However, comparisons of biomarkers between HBV and HCV patients have not previously been reported. The aim of this study was to investigate differences in hematological biomarker in the sera of HBV and HCV patients and to find a key biomarker to differentiate between HBV and HCV infections. HBV (n=115) and HCV (n=128) samples (serum and whole blood) were collected and tested using a biochemical analysis system. The obtained data were analyzed with SPSS 18.0 statistical software. The mean age of the HCV group (60.3±14.1) was much higher than that of the HBV group (51.1±12.4). Male and female rates were 71.3% and 28.7% in the HBV group and 53.9% and 46.1% in the HCV group, respectively (p = 0.005). AST, ALT, and TG values were higher in the HCV group than in the HBV group. Although γ-GTP and LDL levels were higher in the HBV group than in the HCV group, apoB and apoE levels were much higher in HCV group than in HBV group (p < 0.001). There were no significant differences in the other hematological biomarkers between the HBV and HCV groups. In conclusion, HBV rates were higher in male patients, and HCV rates were higher in older patients. In particular, apoE and apoB were more highly expressed in HCV patients, and they might be key markers to differentiate HCV infection.
Apolipoproteins B ; Apolipoproteins E ; Apolipoproteins* ; Biomarkers ; Carcinoma, Hepatocellular ; Cholesterol* ; Female ; Hepacivirus* ; Hepatitis B virus* ; Hepatitis B* ; Hepatitis C* ; Hepatitis* ; Humans ; Korea* ; Liver ; Liver Cirrhosis ; Male

BACKGROUND: Apolipoprotein A2 (APO A2) is the second most abundant structural apolipoprotein in high density lipoprotein. Several studies have examined the possible effect of APO A2 on atherosclerosis incidence. Due to the role of inflammation in atherosclerosis, we aimed to determine the relationship between APO A2 -265T/C polymorphism and inflammation as a risk factor in type 2 diabetes mellitus (T2DM) patients. METHODS: In total, 180 T2DM patients, with known APO A2 -265T/C polymorphism, were recruited for this comparative study and were grouped equally based on their genotypes. Dietary intakes, anthropometric parameters, lipid profile, and inflammatory markers (i.e., pentraxin 3 [PTX3], high-sensitivity C-reactive protein [hs-CRP], and interleukin 18) were measured. The data were analyzed using an independent t-test, a chi-square test, and the analysis of covariance. RESULTS: After adjusting for confounding factors, in the entire study population and in the patients with or without obesity, the patients with the CC genotype showed higher hs-CRP (P=0.001, P=0.008, and P=0.01, respectively) and lower PTX3 (P=0.01, P=0.03, and P=0.04, respectively) in comparison with the T allele carriers. In the patients with the CC genotype, no significant differences were observed in the inflammatory markers between the obese or non-obese patients. However, regarding the T allele carriers, the plasma hs-CRP level was significantly higher in the obese patients compared to the non-obese patients (P=0.01). CONCLUSION: In the T2DM patients, the CC genotype could be considered as a risk factor and the T allele as a protective agent against inflammation, which the latter effect might be impaired by obesity. Our results confirmed the anti-atherogenic effect of APO A2, though more studies are required to establish this effect.
Alleles ; Apolipoprotein A-II* ; Apolipoproteins ; Atherosclerosis ; C-Reactive Protein ; Diabetes Mellitus, Type 2* ; Genotype ; Humans ; Incidence ; Inflammation ; Interleukins ; Lipoproteins ; Obesity ; Plasma ; Risk Factors