1.Rapid Changes in Serum Lipid Profiles during Combination Therapy with Daclatasvir and Asunaprevir in Patients Infected with Hepatitis C Virus Genotype 1b.
Takeshi CHIDA ; Kazuhito KAWATA ; Kazuyoshi OHTA ; Erika MATSUNAGA ; Jun ITO ; Shin SHIMOYAMA ; Satoru YAMAZAKI ; Hidenao NORITAKE ; Tetsuro SUZUKI ; Takafumi SUDA ; Yoshimasa KOBAYASHI
Gut and Liver 2018;12(2):201-207
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
2.Investigation of the relationship between apolipoprotein gene polymorphism and hepatitis B virus infection in China.
Zhi-Nong YIN ; Xin ZHOU ; Shen-Kai YAN ; Jun-Wen WANG ; Qing-Ling MENG ; Wei LIU
Chinese Journal of Experimental and Clinical Virology 2012;26(1):28-30
OBJECTIVETo explore the gene polymorphisms of ApoAI-75 Msp1, ApoB Msp1, ApoCIII Sst1, LRP5, and ApoE genotypes in two pairs of semi different modes of hepatitis B for HBV markers.
METHODSThe patients are divided into 9 groups. There were a total of 720 cases, 80 patients in each group, The patients was carried out by SnaPshot method (single-base multilocus micro-sequencing), and different genotypes of each locus were conducted by the method of sequencing in order to support the final evidence of the accuracy of test results.
RESULTSThere was association between gene polymorphisms of ApoAI-75Msp1 and ApoE and different modes of two pairs of semi-hepatitis B (P < 0.05), while there wasn't any association between gene polymorphisms of ApoB-Msp1, ApoCIII-Sst1, LRP5 and different modes of two pairs of semi-hepatitis B (P > 0.05).
CONCLUSIONThe gene polymorphism of ApoAI-75Msp1 and ApoE was associated with the different modes of HBV markers.
Apolipoprotein A-I ; genetics ; Apolipoprotein C-III ; genetics ; Apolipoproteins ; genetics ; Apolipoproteins B ; genetics ; China ; Genotype ; Hepatitis B ; genetics ; Humans ; Polymorphism, Genetic
3.Abnormalities of Serum Lipid, Lipoprotein and Apolipoprotein in Both Normotriglyceridemic and Hypertriglyceridemic Patients with Chronic Renal Failure on Chronic Hemodialysis.
Kyu Sung CHO ; Gyeong Ran CHOI ; Seung Jung KEE ; Soo Hyun KIM ; Myung Geun SHIN ; Jong Hee SHIN ; Soon Pal SUH ; Dong Wook RYANG
Korean Journal of Clinical Pathology 1999;19(4):414-419
BACKGROUND: Hypertriglyceridemia (HTG) has been considered a characteristic plasma lipid abnormality in hemodialysis patients with chronic renal failure, but is actually shown in only some of them (30-50%). Also renal dyslipidemia may contribute to atherosclerosis in hemodialysis patients. METHODS: Study population consisted of 34 patients with normotriglyceridemia (NTG), 11 patients with HTG and 47 controls. We measured total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), apolipoprotein (apo) A-I, apoB, apoC-III and apoE. RESULTS: Compared with controls, the NTG patients had significantly decreased levels of TC, HDL-C, and low density lipoprotein-cholesterol (LDL-C). But HTG patients had significantly increased TG, and TC/HDL-C ratio which were considered to represent the atherogenic indicator and had decreased HDL-C and LDL-C (P <0.001), with significant increase of TG and TC/HDL-C ratio compared with those of NTG patients. In the apolipoprotein profiles, all patients showed decreased levels of apoA-I, apoB, and apoA-I/apoC-III ratio and increased levels of apoC-III and apoC-III/apoE ratio compared with those of controls (P <0.001). Especially, HTG patients had significantly increased levels of apoC-III compared with NTG patients. CONCLUSIONS: So these results indicated that abnormalities of those potentially atherogenic lipid and lipoproteins may contribute to the high incidence of cardiovascular diseases and progression of renal disease in the HTG patients than NTG patients on maintenance hemodialysis.
Apolipoprotein A-I
;
Apolipoprotein C-III
;
Apolipoproteins B
;
Apolipoproteins E
;
Apolipoproteins*
;
Atherosclerosis
;
Cardiovascular Diseases
;
Cholesterol
;
Dyslipidemias
;
Humans
;
Hypertriglyceridemia
;
Incidence
;
Kidney Failure, Chronic*
;
Lipoproteins*
;
Plasma
;
Renal Dialysis*
;
Triglycerides
4.Comparative Analysis of Serum Proteomes of Moyamoya Disease and Normal Controls.
Eun Jeong KOH ; Han Na KIM ; Tian Ze MA ; Ha Young CHOI ; Yong Geun KWAK
Journal of Korean Neurosurgical Society 2010;48(1):8-13
OBJECTIVE: The etiology and pathogenesis of moyamoya disease remain unclear. Furthermore, the definitive diagnostic protein-biomarkers for moyamoya disease are still unknown. The present study analyzed serum proteomes from normal controls and moyamoya patients to identify novel serological biomarkers for diagnosing moyamoya disease. METHODS: We compared the two-dimensional electrophoresis patterns of sera from moyamoya disease patients and normal controls and identified the differentially-expressed spots by matrix-assisted laser desorption/ionization-time-of flight mass spectrometry and electrospray ionization quadruple time-of-flight mass spectrometry. RESULTS: We found and analyzed 22 differently-expressed proteomes. Two proteins were up-regulated. Twenty proteins were down-regulated. Complement C1 inhibitor protein and apolipoprotein C-III showed predominantly changed expressions (complement C1 inhibitor protein averaged a 7.23-fold expression in moyamoya patients as compared to controls, while apolipoprotein C-III averaged a 0.066-fold expression). CONCLUSION: Although our study had a small sample size, our proteomic data provide serologic clue proteins for understanding moyamoya disease.
Apolipoprotein C-III
;
Biomarkers
;
Complement C1 Inhibitor Protein
;
Electrophoresis
;
Humans
;
Mass Spectrometry
;
Moyamoya Disease
;
Proteins
;
Proteome
;
Sample Size
5.Hypertriglyceridemia and Cardiovascular Diseases: Revisited.
Seung Hwan HAN ; Stephen J NICHOLLS ; Ichiro SAKUMA ; Dong ZHAO ; Kwang Kon KOH
Korean Circulation Journal 2016;46(2):135-144
Residual cardiovascular risk and failure of high density lipoprotein cholesterol raising treatment have refocused interest on targeting hypertriglyceridemia. Hypertriglyceridemia, triglyceride-rich lipoproteins, and remnant cholesterol have demonstrated to be important risk factors for cardiovascular disease; this has been demonstrated in experimental, genetic, and epidemiological studies. Fibrates can reduce cardiovascular event rates with or without statins. High dose omega-3 fatty acids continue to be evaluated and new specialized targeting treatment modulating triglyceride pathways, such as inhibition of apolipoprotein C-III and angiopoietin-like proteins, are being tested with regard to their effects on lipid profiles and cardiovascular outcomes. In this review, we will discuss the role of hypertriglyceridemia, triglyceride-rich lipoproteins and remnant cholesterol on cardiovascular disease, and the potential implications for treatment stargeting hypertriglyceridemia.
Apolipoprotein C-III
;
Cardiovascular Diseases*
;
Cholesterol
;
Cholesterol, HDL
;
Epidemiologic Studies
;
Fatty Acids, Omega-3
;
Fibric Acids
;
Hydroxymethylglutaryl-CoA Reductase Inhibitors
;
Hypertriglyceridemia*
;
Lipoproteins
;
Risk Factors
;
Triglycerides
6.Adverse factors increase preeclampsia-like changes in pregnant mice with abnormal lipid metabolism.
Xiaoyan DING ; Zi YANG ; Yiwei HAN ; Huan YU
Chinese Medical Journal 2014;127(15):2814-2818
BACKGROUNDPreeclampsia (PE) is a multifactorial pregnancy complication. Maternal underlying condition and adverse factors both influence the pathogenesis of PE. Abnormal lipid metabolism as a maternal underlying disease may participate in the occurrence and development of PE. This study aimed to observe the effects of adverse factors on PE-like symptoms of pregnant mice with genetic abnormal lipid metabolism.
METHODSApolipoprotein C-III (ApoC3) transgenic mice with abnormal lipid metabolism were subcutaneously injected with L-arginine methyl ester (L-NAME) or normal saline (NS) daily starting at Day 7 or 16 of pregnancy (ApoC3+L-NA and ApoC3+NS groups), and wild-type (WT) mice served as a control (WT+L-NA and WT+NS groups). All mice were subdivided into early and late subgroups by injection time. The mean arterial pressure (MAP) and urinary protein were measured. Pregnancy outcomes, including fetal weight, placental weight, live birth rate, and fetal absorption rate, were analyzed. Pathologic changes in the placenta were observed by hematoxylin-eosin staining. One-way analysis of variance, t-test, and χ(2) test were used for statistical analysis.
RESULTSMAP significantly increased for ApoC3+NS groups compared with WT+NS groups (P < 0.05), without significant difference in urine protein. Following L-NAME injection, MAP and urinary protein significantly increased for ApoC3+L-NA and WT+L-NA compared with the corresponding NS groups (P < 0.05), and the increase for ApoC3+L-NA was more obvious. Urinary protein levels in early ApoC3+L-NA and WT+L-NA significantly increased compared with the corresponding late groups (P < 0.05). Fetal absorption rate significantly increased and fetal and placental weights significantly decreased in early ApoC3+L-NA and WT+L-NA compared with the corresponding NS groups (P < 0.05), without significant difference in late ApoC3+L-NA and WT+L-NA groups. Fetal weight in early ApoC3+L-NA was significantly lower than in early WT+L-NA group (P < 0.05). Morphologic examination of placentas from early ApoC3+L-NA and WT+L-NA groups showed varying degrees of fibrinoid necrosis.
CONCLUSIONSApoC3 transgenic mice with abnormal lipid metabolism showed gestational hypertension. Adverse factors and early effect time could aggravate the PE-like symptoms for ApoC3 transgenic mice.
Animals ; Apolipoprotein C-III ; genetics ; metabolism ; Female ; Lipid Metabolism ; drug effects ; genetics ; Male ; Mice ; Mice, Transgenic ; NG-Nitroarginine Methyl Ester ; pharmacology ; Pre-Eclampsia ; genetics ; metabolism ; Pregnancy
7.Neither polyphenol-rich red wine nor fenofibrate affects the onset of type-1 diabetes mellitus in the BB rat.
Karin ÅVALL ; Per Olof BERGGREN ; Lisa JUNTTI-BERGGREN
Laboratory Animal Research 2018;34(3):126-131
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*
8.The role of apolipoprotein C3 in the regulation of nonalcoholic fatty liver disease, glucose and lipid metabolism, and islet β cell function.
Shan YAN ; Zhi-Yong DING ; Yuan GAO ; Wang-Jia MAO ; Xiao-Yun CHENG
Acta Physiologica Sinica 2023;75(6):767-778
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*
9.Polymorphisms in the apolipoprotein A5 gene and apolipoprotein C3 gene in patients with coronary artery disease.
Nan BI ; Sheng-Kai YAN ; Guo-Ping LI ; Zhi-Nong YIN ; Hong XUE ; Gang WU ; Bao-Sheng CHEN
Chinese Journal of Cardiology 2005;33(2):116-121
OBJECTIVETo investigate the association between the -1131T/C and 56C/G polymorphism in the APOA5 gene as well as the -482C/T in the APOC3 gene and susceptibility to coronary artery disease (CAD) in a Chinese Han population.
METHODSUsing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and polyacrylamide gel electrophoresis (PAGE) methods, we analyzed the genotypes in 312 CAD patients diagnosed by angiography and 317 healthy controls. The levels of serum lipid profiles were also studied by biochemical methods.
RESULTSThe frequency of the APOA5 -1131 C allele in CAD patients was significantly higher than that of the control group (39.9% vs. 33.3%, P = 0.02). Compared with the wild type TT, CC homozygotes had a significantly increased CAD risk (OR = 1.93 and OR = 1.80 using unadjusted and adjusted logistic regression models, respectively). This association still existed after adjustment for the APOC3-482 variant. The APOA5-1131C allele also showed a correlation with increasing plasma TG levels (P < 0.01).
CONCLUSIONSThe APOA5-1131T/C polymorphism but not APOC3-482C/T might contribute to an increased risk of CAD among Chinese accompanied by an elevation of serum TG levels; this effect was found to be independent of the APOC3-482C/T variant.
Adult ; Aged ; Aged, 80 and over ; Alleles ; Apolipoprotein A-V ; Apolipoprotein C-III ; genetics ; Apolipoproteins A ; genetics ; Asian Continental Ancestry Group ; genetics ; Coronary Artery Disease ; blood ; genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Triglycerides ; blood
10.Gel electrophoresis analysis on plasma differential protein in patients with unstable angina of blood-stasis pattern.
Hui-Hui ZHAO ; Jian-Xin CHEN ; Qi SHI
Chinese Journal of Integrated Traditional and Western Medicine 2010;30(5):488-492
OBJECTIVETo seek the plasma differential proteins in patients with unstable angina of blood-stasis pattern (UA-BSS) for exploring the proteomic specialty in them by way of two-dimensional difference gel electrophoresis (DIGE) detection on plasma of patients and healthy persons.
METHODSUsing DIGE and tandem mass spectrometry, comparative proteomic study was conducted on the plasma of 12 UA patients of qi-deficiency and blood-stasis pattern (UA-QBS), 12 UA patients of phlegm-stasis cross-blocking pattern (UA-PSS) and 12 healthy volunteers.
RESULTSPreliminary results showed that Haptoglobin beta chain, DBP, HBB, HBA, Transthyretin, ApoA- I, ApoA-IV were significantly differentially expressed in both patterns, while Haptoglobin alpha1 chain, alpha-1-acid glycoprotein, ApoC-III, ApoA-II, ApoC-II, ApoJ, and Haptoglobin alpha 2 chain were only seen differentially expressed in the UA-PSS patients, alpha1-antitrypsin, Fibrinogen gamma chain, and Fibrin beta were only seen differentially expressed in UA-QBS patients.
CONCLUSIONThe common proteomics characteristics of patients of QBS and PSS patterns may be correlated with inflammatory reaction and metabolic disturbance (including blood lipid and blood oxygen).
Aged ; Angina, Unstable ; blood ; diagnosis ; Apolipoprotein A-II ; blood ; Apolipoprotein C-III ; blood ; Blood Proteins ; metabolism ; Case-Control Studies ; Female ; Fibrinogen ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Proteome ; analysis ; Proteomics ; Two-Dimensional Difference Gel Electrophoresis