Animals ; Arteriosclerosis ; blood ; Blood Glucose ; metabolism ; Cholesterol ; blood ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Coronary Artery Disease ; blood ; Fatty Liver ; blood ; Humans ; Triglycerides ; blood

PURPOSE: Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low density lipoprotein receptor (LDLR) and promotes degradation of the LDLR. Inhibition of PCSK9 either by reducing its expression or by blocking its activity results in the upregulation of the LDLR and subsequently lowers the plasma concentration of LDL-cholesterol. As a modality to inhibit PCSK9 action, we searched the chemical library for small molecules that block the binding of PCSK9 to the LDLR. MATERIALS AND METHODS: We selected 100 chemicals that bind to PCSK9 where the EGF-AB fragment of the LDLR binds via in silico screening of the ChemBridge chemical library, using the computational GOLD algorithm analysis. Effects of chemicals were evaluated using the PCSK9-LDLR binding assay, immunoblot analysis, and the LDL-cholesterol uptake assay in vitro, as well as the fast performance liquid chromatography assay for plasma lipoproteins in vivo. RESULTS: A set of chemicals were found that decreased the binding of PCSK9 to the EGF-AB fragment of the LDLR in a dose-dependent manner. They also increased the amount of the LDLR significantly and subsequently increased the uptake of fluorescence-labeled LDL in HepG2 cells. Additionally, one particular molecule lowered the plasma concentration of total cholesterol and LDL-cholesterol significantly in wild-type mice, while such an effect was not observed in Pcsk9 knockout mice. CONCLUSION: Our findings strongly suggest that in silico screening of small molecules that inhibit the protein-protein interaction between PCSK9 and the LDLR is a potential modality for developing hypercholesterolemia therapeutics.
Animals ; Cholesterol/*blood ; Cholesterol, LDL/blood ; Hep G2 Cells ; Humans ; Mice ; Mice, Knockout ; Proprotein Convertases/*metabolism ; Receptors, LDL/*metabolism ; Serine Endopeptidases/*metabolism ; *Small Molecule Libraries

OBJECTIVETo study the effect of liposuction on insulin resistance and lipid metabolism.

METHODSThe levels of serum triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and insulin sensitivity were measured pre-and 2-4 months postoperatively in 20 consecutive patients undergoing liposuction.

RESULTSCompared with preoperative, the insulin sensitivity increased significantly, the levels of TC and LDL-C decreased after the liposuction procedure.

CONCLUSIONSLiposuction may improve the insulin resistance and lipid metabolism.

Adult ; Blood Glucose ; metabolism ; Cholesterol ; blood ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Female ; Humans ; Insulin Resistance ; Lipectomy ; Lipid Metabolism ; Middle Aged ; Triglycerides ; blood ; Young Adult

Resistin, a newly discovered peptide hormone mainly secreted by adipose tissues, is present at high levels in serum of obese mice and may be a potential link between obesity and insulin resistance in rodents. However, some studies of rat and mouse models have associated insulin resistance and obesity with decreased resistin expression. In humans, no relationship between resistin level and insulin resistance or adiposity was observed. This suggests that additional studies are necessary to determine the specific role of resistin in the regulation of energy metabolism and adipogenesis. In the present study, we investigated the effect of resistin in vivo on glucose and lipid metabolism by over-expressing resistin in mice by intramuscular injection of a recombinant eukaryotic expression vector pcDNA3.1-Retn encoding porcine resistin gene. After injection, serum resistin and serum glucose (GLU) levels were significantly increased in the pcDNA3.1-Retn-treated mice; there was an obvious difference in total cholesterol (TC) level between the experiment and the control groups on Day 30. In pcDNA3.1-Retn-treated mice, both free fatty acid (FFA) and high density lipoprotein (HDL) cholesterol levels were markedly lower than those of control, whereas HDL cholesterol and triglyceride (TG) levels did not differ between the two groups. Furthermore, lipase activity was expressly lower on Day 20. Our data suggest that resistin over-expressed in mice might be responsible for insulin resistance and parameters related to glucose and lipid metabolism were changed accordingly.
Animals ; Blood Glucose ; analysis ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Fatty Acids, Nonesterified ; blood ; Glucose ; metabolism ; HeLa Cells ; Humans ; Lipid Metabolism ; Male ; Mice ; Resistin ; blood ; physiology ; Triglycerides ; blood

OBJECTIVE To investigate the relationship between the Nco I, Ava II polymorphism of low density lipoprotein receptor (LDL-R) gene in patients with the occurrence of atherosclerotic cerebral infarction (ACI) among the Han nationality in Liaoning province. METHODS The polymerase chain reaction technique was used to study the polymorphisms of LDL-R gene and allele frequencies in 77 patients with ACI and in 113 age-matched Chinese healthy controls. The levels of the lipid and lipoproteins were also compared among the cases with ACI and the controls. RESULTS A(+) frequencies of LDL-R gene in healthy controls and ACI group were 0.230 and 0.125 respectively, while the N(+) frequencies of healthy control and ACI group was 0.667 and 0.662 respectively. In case of the coexistence of A(-) A(-) and N(+) N(+), the relative risk (RR) of ACI was 5.56(P<0.001), while the RR of the increase of serum levels TG, TC, LDL-C, LP(a) were 4.29, 7.67, 9.33 and 3.09(P<0.05), respectively. CONCLUSION The coexistence of A(-) A(-) and N(+) N(+) can affect the concentration of lipid and lipoprotein and is in close relationship with the occurrence of ACI.
Apolipoprotein A-I ; blood ; Apolipoproteins B ; blood ; Binding Sites ; genetics ; Cerebral Infarction ; blood ; genetics ; Cholesterol ; blood ; Cholesterol, LDL ; blood ; DNA ; genetics ; metabolism ; Deoxyribonucleases, Type II Site-Specific ; metabolism ; Genotype ; Humans ; Intracranial Arteriosclerosis ; blood ; genetics ; Lipoproteins ; blood ; Receptors, LDL ; genetics ; Triglycerides ; blood

Animals ; Aorta ; pathology ; Atherosclerosis ; blood ; etiology ; metabolism ; Chemokine CCL2 ; metabolism ; Cholesterol ; blood ; Cholesterol, Dietary ; administration & dosage ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Dehydroepiandrosterone ; pharmacology ; Diet, Atherogenic ; Immunohistochemistry ; Rabbits ; Random Allocation ; Triglycerides ; blood ; Vascular Cell Adhesion Molecule-1 ; metabolism

This study was aimed to examine the effect of ovariectomy on visceral fat, serum adiponectin levels and lipid profile. Forty-five female Sprague Dawley rats were divided into three groups (n=15 each): ovariectomized group (OVX), ovariectomized plus estrogen-treated group (OVX+E2), and sham-operated group (SHAM). Body weight, abdominal adipose tissues, serum adiponectin and lipid profile were measured and compared among the groups after three-month feeding post-surgery. Significant increases in body weight and visceral fat were found in ovariectomized rats when compared with sham-operated ones and significant increases were also observed in serum adiponectin, triglyceride and very low density lipoprotein cholesterol levels in ovariectomized rats. Body weight, visceral fat and serum adiponectin levels were profoundly reduced in OVX+E2 group as compared with OVX group. It was concluded that ovarian hormone deficiency induced by ovariectomy leads to significant increases in body weight and visceral fat, along with increased serum adiponectin, triglyceride and very low density lipoprotein cholesterol levels in rats. Attenuation in these changes can be achieved by estrogen supplementation.
Adiponectin ; blood ; Animals ; Cholesterol, LDL ; blood ; Female ; Intra-Abdominal Fat ; metabolism ; Ovariectomy ; Rats ; Rats, Sprague-Dawley ; Triglycerides ; blood

OBJECTIVE: To explore the effect of niacin on the serum adiponectin concentration in hypercholesterolemia rabbit and the adiponectin concentration secreted by adipocytes in normal rabbits. METHODS: Ten male New Zealand white rabbits fed with high cholesterol diet for 8 weeks were randomly divided into 2 groups: (1) The high cholesterol group maintained a high cholesterol diet for 8 weeks. (2) The same cholesterol diet plus niacin (0.4g/kg*d ) were administrated for 6 weeks in the niacin group. A control group was fed with normal diet for 14 weeks. Subcutaneous adipose from the control group was collected for adipocyte culture. Matured adipocytes were incubated with various concentrations of niacin (0, 0.25, 0.5, 1.0, and 2.0micromol/L). Adiponectin concentrations in the serum and adipocyte culture supernatant were measured by enzyme-linked-immunosorbent assay. RESULTS: Compared with the control group, rabbits in the high cholesterol group showed higher serum levels of total cholesterol, and low density lipoprotein cholesterol (LDL-C), all of which were significantly reduced by niacin treatment (P<0.01),and serum high density lipoprotein-cholesterol (HDL-C) significantly increased (P<0.01). At 8th week, the mean adiponectin concentration of rabbits fed with high cholesterol diet was significantly lower than that of the control group[(1.268+/-0.039)mg/L vs.(1.449+/-0.107)mg/L,P<0.01]. Niacin treatment significantly elevated the serum adiponectin level which was positively related to HDL-C,and negatively related to TC and LDL-C. Cell experiment in vitro indicated that niacin could significantly induce the adiponectin secretion of adipocytes in a dose-dependent manner. CONCLUSION Niacin can significantly promote the adiponectin secretion of adipocytes, suggesting that niacin probably has an ability of elevating the serum adiponectin level in addition to lipid-lowering effect.
Adipocytes ; cytology ; drug effects ; metabolism ; Adiponectin ; blood ; metabolism ; Animals ; Cholesterol ; blood ; Cholesterol, Dietary ; administration & dosage ; toxicity ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Dose-Response Relationship, Drug ; Hypercholesterolemia ; blood ; etiology ; prevention & control ; Hypolipidemic Agents ; pharmacology ; Male ; Niacin ; pharmacology ; Rabbits ; Random Allocation

OBJECTIVETo determine whether blood lipids profile, fibrinogen and viscosity were associated with passive smoking (i. e. environmental tobacco smoke, ETS) in Chinese women who never smoke.

METHODSIn Xi'an, China, a case-control study was carried out on 115 cases of coronary heart disease (CHD) defined by coronary arteriography (CAG) and 208 non-CHD controls confirmed by CAG and/or exercise electrocardiography. Data on exposure to ETS, defined as exposure from cigarettes smoking husband or co-workers or both for at least 5 years, was obtained through standardized interviews. Standard laboratory methods were used and the lipid measurements were under US CDC quality control programs.

RESULTSIn the subjects defined by CAG, the levels of high density lipoprotein cholesterol (HDL-C), HDL2C, apolipoprotein (apo) A1 among passive smokers appeared lower than those in non-passive smokers,but the low density lipoprotein cholesterol (LDL-C), apoB, apoB/A1, fibrinogen, plasma and whole blood viscosity were higher than that in non-passive smokers. There were positive associations of the numbers of coronary arteriosclerosis with the levels of blood lipids,fibrinogen and viscosity. In the non-CHD controls, 81 subjects were not exposed and 127 were exposed to ETS. The P values of t-test for the adjusted (for age, body mass index, present diseases history) means between two groups were listed below: 0.06 (total cholesterol), 0.30 (triglyceride), 0.004 (HDL-C), <0.001 (HDL2-C), < 0.001 (apoA1), 0.009 (apoB), <0.001 (apoB/apoA1), <0.001 (fibrinogen), <0.001 (plasma viscosity), <0.001 and 0.004 [two measures (5.75/s and 230/s) of whole blood viscosity]. The correlation coefficients between cumulative exposure of passive smoking and HDL-C,HDL2-C,apoA1, apoB, apoB/apoA1, fibrinogen, plasma viscosity, and two measures of whole blood viscosity were -0.25, -0.27, -0.30, 0.24, 0.31, 0.32, 0.43, 0.51 and 0.36 (all P<0.01), respectively.

CONCLUSIONPassive smoking could affect blood lipid metabolism, fibrinogen and viscosity in the never smoking women which might contribute to the causation of coronary heart disease.

Apolipoprotein A-I ; blood ; Blood Viscosity ; drug effects ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Coronary Disease ; etiology ; Female ; Fibrinogen ; metabolism ; Humans ; Male ; Middle Aged ; Tobacco Smoke Pollution ; adverse effects

OBJECTIVETo observe the intervention effects of Liandou Qingmai Recipe (LQR) on atherogenic indices of plasma (AIP) and high-sensitivity c-reactive protein (hs-CRP) level in patients with coronary heart disease (CHD).

METHODSSixty-eight CHD patients were randomly assigned to two groups, 35 patients in the treatment group and 33 in the control group, all were treated by the regular CHD treatment, but to patients in the treatment group, LQR was given additionally. AIP value was calculated before and after treatment through measuring plasma levels of triglyceride (TG), high-density and low-density lipoprotein cholesterol (HDL-C and LDL-C). Besides, the levels of hs-CRP and peripheral blood leucocyte (PBL) were observed as well.

RESULTSNo significant difference existed between groups in all the detected parameters before treatment (P > 0.05). After treatment, levels of LDL-C, HDL-C, hs-CRP and PBL lowered significantly in the control group, but the changes of AIP and TG were insignificant (P > 0.05); while in the treatment group, all the parameters lowered significantly, with the levels of AIP, TG, hs-CRP and PBL significantly lower than those in the control group respectively (P < 0.05).

CONCLUSIONLQR can decrease levels of AlP and hs-CRP in CHD patients, amplify the diameters of LDL-C granule, and further lower hs-CRP and PLB levels, showing anti-atherosclerosis and anti-inflammation effects.

Aged ; Aged, 80 and over ; Biomarkers ; blood ; C-Reactive Protein ; metabolism ; Cholesterol ; blood ; Cholesterol, LDL ; blood ; Coronary Artery Disease ; blood ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Lipoproteins, LDL ; blood ; Male ; Middle Aged ; Phytotherapy ; Risk Factors ; Triglycerides ; blood