Monocyte to high-density lipoprotein cholesterol ratio as a predictor of the activity of thyroid-associated ophthalmopathy

AIM:To evaluate the relationship between monocyte to high-density lipoprotein cholesterol ratio(MHR)and the disease activity of thyroid-associated ophthalmopathy(TAO).METHODS:A total of 87 patients were classified into two groups based on clinical activity score(CAS)scoring criteria:high CAS group(n=62,the CAS score was≥3);low CAS group(n=25,the CAS score was<3).In addition,a group of healthy people(n=114)were included to compared the MHR.Proptosis,MHR,average signal intensity ratio(SIR),average lacrimal gland(LG)-SIR,average extraocular muscles(EOM)area from 87 patients with TAO were calculated in magnetic resonance imaging(MRI),and compared between these two groups.Correlation testing was utilized to evaluate the association of parameters among the clinical variables.RESULTS:Patients in high CAS group had a higher proptosis(P=0.041)and MHR(P=0.048).Compared to the healthy group,the MHR in the TAO group was higher(P=0.001).Correlation testing declared that CAS score was strongly associated with proptosis and average SIR,and MHR was positively associated with CAS score,average SIR,and average LG-SIR.The area under the receiver operating characteristic curve(AUC)of MHR was 0.6755.CONCLUSION:MHR,a novel inflammatory biomarker,has a significant association with CAS score and MRI imaging(average SIR and LG-SIR)and it can be a new promising predictor during the active phase of TAO.

Correlation of Helicobacter pylori infection with high-density lipoprotein cholesterol levels and pulse wave conduction velocity

Background:Helicobacter pylori(HP)is associated with several gastrointestinal diseases,including peptic ulcer diseases and gastric cancer,and non-gastrointestinal diseases such as hypertension and Alzheimer's disease.However,the relationship between HP and lipid metabolism and atherosclerosis remains unclear.This study aims to investigate the association between H.pylori infection and high-density lipoprotein cholesterol levels and pulse wave conduction velocity.Methods:This is a report of a cross-sectional study that collected data from 2,827 participants.The data collected included results of life questionnaires,laboratory tests,13C-urea breath test(13C-UBT),and pulse wave conduction velocity test.Based on the results of the 13C-UBT test,the subjects were divided into two groups:the HP-uninfected group(HP−)and the HP-infected group(HP+).The study compared the differences in HDL-C levels and brachial-ankle pulse wave velocity(baPWV)between the two groups.One-way regression analysis was used to identify potential factors affecting HDL-C levels in the study population.Multiple regression equations were presented to analyze whether HP infection was an independent risk factor for abnormal HDL-C metabolism in the population.Results:Univariate analysis demonstrated that high-density lipoprotein cholesterol(HDL-C)levels were significantly lower in the HP+group compared to the HP−group,with a mean difference ofβ=−18.1 mg/dl(95%CI:−19.3 to−17.0,P<0.001).After adjusting for all variables,the HDL-C levels remained lower in the HP+group compared to the HP-group,with a mean difference ofβ=−17.4 mg/dl(95%CI:−18.2 to−16.7,P<0.001).These findings suggest that H.pylori infection is independently associated with abnormal HDL-C metabolism.Additionally,brachial-ankle pulse wave velocity(baPWV)was higher in the HP+group than in the HP−group on both sides.On the right side,the baPWV was 1,713.4±231.4 cm/s in the HP+group compared to 1,542.8±237.5 cm/s in the HP−group(t=−18.30,P<0.001).On the left side,the baPWV was 1,743.7±238.8 cm/s in the HP+group compared to 1,562.8±256.3 cm/s in the HP−group(t=−18.23,P<0.001).These results indicate a significant association between H.pylori infection and increased arterial stiffness,as measured by baPWV.Conclusion:Helicobacter pylori infection is associated with a decrease in high-density lipoprotein cholesterol levels and an increase in pulse wave conduction velocity.

Coexistence of High Fibrinogen and Low High-density Lipoprotein Cholesterol Levels Predicts Recurrent Cerebral Venous Thrombosis

Background： Cerebral venous thrombosis （CVT） may lead to serious neurological disorders; however, little is known about the risk factors for recurrent CVT. Our aim was to determine the association between elevated fibrinogen and decreased high-density lipoprotein cholesterol （HDL-C） levels with recurrent CVT. Methods： This retrospective cohort study included participants if they had a first episode of objectively defined CVT and were admitted to Xuan Wu Hospital, Capital Medical University from August 2005 to September 2009. Demographic and clinical variables were collected, as well as laboratory parameters, inchiding plasma fibrinogen and HDL-C. Patients with CVT were tbllowed for recurrent symptomatic CVT. Follow-up was through the end of September 2010. Potential predictors of recurrence were analyzed using Cox survival analysis. Results： At tile end of the lbllow-up, 95 patients were eligible lbr the study. Twelve of 95 patients （12.6%） had recurred CVT. Tile median time of recurrence was 7 months （range： 1-39 months）. Eight of these 12 （66.7%） experienced rectirrence within the first 12 months alter their initial CVT. The recurrence rate of CVT was 2.76 per 100 patient-years. Multivariate Cox regression analysis demonstrated that the coexistence of high fibrinogen （〉4.00 g/L） and low HDL-C （〈1.08 mmol/L） levels at baseline was the only independent predictor for recurrent CVT （hazard ratio： 4.69; 95% confidence interval： 1.10-20,11; P 〈 0.05）. Of tile twelve patients with recurrent CVT in our study, 7 （58.3%） had high fibrinogen plus low HDL-C levels. All 7 of these patients took warfarin for 3-12 months, and 6 of 7 had rectirrent CVT after the discontinuation of anticoagulant treatment. Conclusions： Concomitant high fibrinogen and low HDL-C levels may be associated with recurrence of CVT. The ett＇ect of potential risk lhctors related to atherothrombosis on rectinent CVT should be closely monitored.

Reduced serum high-density lipoprotein cholesterol levels and aberrantly expressed cholesterol metabolism genes in colorectal cancer

BACKGROUND Colorectal cancer(CRC)is a common malignant tumor of the gastrointestinal tract.Lipid metabolism,as an important part of material and energy circulation,is well known to play a crucial role in CRC.AIM To explore the relationship between serum lipids and CRC development and identify aberrantly expressed cholesterol metabolism genes in CRC.METHODS We retrospectively collected 843 patients who had confirmed CRC and received surgical resection from 2013 to 2015 at the Cancer Hospital of the Chinese Academy of Medical Sciences as our research subjects.The levels of serum total cholesterol(TC),triglycerides,low-density lipoprotein cholesterol(LDL-C),highdensity lipoprotein cholesterol(HDL-C),LDL-C/HDL-C and clinical features were collected and statistically analyzed by SPSS.Then,we used the data from Oncomine to screen the differentially expressed genes(DEGs)of the cholesterol metabolism pathway in CRC and used Gene Expression Profiling Interactive Analysis to confirm the candidate DEGs.PrognoScan was used to analyze the prognostic value of the DEGs,and Search Tool for the Retrieval of Interacting Genes was used to construct the protein-protein interaction network of DEGs.RESULTS The serum HDL-C level in CRC patients was significantly correlated with tumor size,and patients whose tumor size was more than 5 cm had a lower serum HDL-C level(1.18±0.41 mmol/L vs 1.25±0.35 mmol/L,P<0.01)than their counterparts.In addition,TC/HDL(4.19±1.33 vs 3.93±1.26,P<0.01)and LDL-C/HDL-C(2.83±1.10 vs 2.61±0.96,P<0.01)were higher in patients with larger tumors.The levels of HDL-C(P<0.05),TC/HDL-C(P<0.01)and LDL-C/HDL-C(P<0.05)varied in different stages of CRC patients,and the differences were significant.We screened 14 differentially expressed genes(DEGs)of the cholesterol metabolism pathway in CRC and confirmed that lipoprotein receptor-related protein 8(LRP8),PCSK9,low-density lipoprotein receptor(LDLR),MBTPS2 and FDXR are upregulated,while ABCA1 and OSBPL1A are downregulated in cancer tissue.Higher expression of LDLR(HR=3.12,95%CI:1.77-5.49,P<0.001),ABCA1(HR=1.66,95%CI:1.11-2.48,P=0.012)and OSBPL1A(HR=1.38,95%CI:1.01-1.89,P=0.041)all yielded significantly poorer DFS outcomes.Higher expression of FDXR(HR=0.7,95%CI:0.47-1.05,P=0.002)was correlated with longer DFS.LDLR,ABCA1,OSBPL1A and FDXR were involved in many important cellular function pathways.CONCLUSION Serum HDL-C levels are associated with tumor size and stage in CRC patients.LRP8,PCSK9,LDLR,MBTPS2 and FDXR are upregulated,while ABCA1 and OSBPL1A are downregulated in CRC.Among them,LDLR,ABCA1,OSBPL1A and FDXR were valuable prognostic factors of DFS and were involved in important cellular function pathways.

High-density Lipoprotein Cholesterol and In-hospital Mortality in Patients with Acute Aortic Dissection

The association between high-density lipoprotein cholesterol（HDL-C） and mortality in patients with acute aortic dissection（AAD） is unclear. From January 2007 to January 2014, a total of 928 consecutive AAD patients who were admitted within 48 h after the onset of symptoms were enrolled in the study. Patients were divided into two groups according to whether serum HDL-C level was below the normal lower limit or not. The Cox proportional hazard regression model was used to identify the predictive value of HDL-C for in-hospital mortality in patients with AAD. As compared with normal HDL-C group（n=585）, low HDL-C group（n=343） had lower levels of systolic blood pressure and hemoglobin and higher levels of leukocyte, alanine aminotransferase, blood glucose, blood urea nitrogen, creatinine and urea acid. Low HDL-C group had significantly higher in-hospital mortality than normal HDL-C group（21.6% vs. 12.6%, log-rank=10.869, P=0.001）. After adjustment for baseline variables including demographics and biologic data, the increased risk of in-hospital mortality in low HDL-C group was substantially attenuated and showed no significant difference（adjusted hazard ratio, 1.23; 95% confidence interval, 0.86–1.77; P=0.259）. Low HDL-C is strongly but not independently associated with in-hospital mortality in patients with AAD.

A Possible Mechanism Linking Hyperglycemia and Reduced High-density Lipoprotein Cholesterol Levels in Diabetes

This study investigated the role of glucose in the biogenesis of high-density lipoprotein cholesterol(HDL-C).Mouse primary peritoneal macrophages were harvested and maintained in Dulbecco’s modified Eagle’s medium(DMEM) containing glucose of various concentrations.The cells were divided into 3 groups in terms of different glucose concentrations in the cultures:Control group(5.6 mmol/L glucose),high glucose concentration groups(16.7 mmol/L and 30 mmol/L glucose).ATP-binding cassette transporter A1(ABCA1) mRNA expression in the macrophages was detected by semi-quantitative RT-PCR 24,48 and 72 h after glucose treatment.The results showed that ABCA1 mRNA expression in the 16.7 mmol/L glucose group was not significantly different from that in the control group at all testing time points(P>0.05 for each).In the 30 mmol/L glucose group,macrophage ABCA1 mRNA expression was not changed significantly at 24 h(P=0.14),but was substantially decreased by 40.4% at 48 h(P=0.009) and by 48.1% at 72 h(P=0.015) as compared with that in the control group.It was concluded that ABCA1 is of vital importance for HDL-C biogenesis.High glucose may hamper HDL-C biogenesis by decreasing ABCA1 expression,which contributes to low HDL-C level in diabetes.

Editorial on hemoglobin A1c, blood pressure, and lowdensity lipoprotein cholesterol goals in diabetics

The American Diabetes Association (ADA) 2013 guidelines state that a reasonable hemoglobin A1c goal for many nonpregnant adults with diabetes is less than 7.0% a hemoglobin A1c level of less than 6.5% may be considered in adults with short duration of diabetes, long life expectancy, and no significant cardiovascular disease if this can be achieved without significant hypoglycemia or other adverse effects of treatment. A hemoglobin A1c level less than 8.0% may be appropriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced macrovascular and microvascular complications, extensive comorbidities, and long-standing diabetes in whom the hemoglobin A1c goal is difficult to attain despite multiple glucoselowering drugs including insulin. The ADA 2013 guidelines recommend that the systolic blood pressure in most diabetics with hypertension should be reduced to less than 140 mmHg. These guidelines also recommend use of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in the treatment of hypertension in diabetics unless they are pregnant. Diabetics at high risk for cardiovascular events should have theirserum low-density lipoprotein (LDL) cholesterol lowered to less than 70 mg/dL with statins. Lower-risk diabetics should have their serum LDL cholesterol reduced to less than 100 mg/dL. Combination therapy of a statin with either a fibrate or niacin has not been shown to provide additional cardiovascular benefit above statin therapy alone and is not recommended. Hypertriglyceridemia should be treated with dietary and lifestyle changes. Severe hypertriglyceridemia should be treated with drug therapy to reduce the risk of acute pancreatitis.

Hepatitis C virus clearance and less liver damage in patients with high cholesterol, low-density lipoprotein cholesterol and APOE ε4 allele

BACKGROUND Cholesterol is related to improvements in the rate of sustained virological response and a robust immune response against the hepatitis C virus(HCV).APOE gene polymorphisms regulate cholesterol levels modifying the course of the HCV infection.The relationship between cholesterol,APOE alleles,and the outcome of HCV infection has not been evaluated in the admixed population of Mexico.AIM To investigate the role of APOE-ε2,-ε3,and-ε4 alleles and the metabolic profile in the outcome of HCV infection.METHODS A total of 299 treatment-na?ve HCV patients were included in this retrospective study.Patients were stratified in chronic hepatitis C(CHC)(n=206)and spontaneous clearance(SC)(n=93).A clinical record was registered.Biochemical tests were assessed by dry chemistry assay.APOE genotypes were determined using a Real-Time polymerase chain reaction assay.RESULTS Total cholesterol,low-density lipoprotein cholesterol(LDL-c),triglycerides,and hypercholesterolemia were higher in SC than CHC patients as well as the frequency of the APOEε4 allele(12.4%vs 7.3%).SC patients were overweight(54.8%).Theε4 allele was associated with SC(OR=0.55,95%CI:0.31-0.98,P=0.042)and mild fibrosis(F1-F2)in CHC patients(OR 0.091,95%CI 0.01-0.75,P=0.020).LDL-c≥101.5 mg/dL(OR=0.20,95%CI:0.10-0.41,P<0.001)and BMI≥26.6 kg/m2(OR=0.37,95%CI:0.18-0.76,P<0.001)were associated with SC status;while ALT≥50.5 IU/L was negatively associated(OR=5.67,95%CI:2.69-11.97,P<0.001).CONCLUSION In SC patients,the APOEε4 allele and LDL-c conferred a protective effect in the course of the HCV infection in the context of excess body weight.

High-density lipoprotein endocytosis in endothelial cells

AIM: To describe the way stations of high-density lipoprotein(HDL) uptake and its lipid exchange in endothelial cells in vitro and in vivo. METHODS: A combination of fluorescence microscopy using novel fluorescent cholesterol surrogates and electron microscopy was used to analyze HDL endocytosis in great detail in primary human endothelial cells. Further, HDL uptake was quantified using radio-labeled HDL particles. To validate the in vitro findings mice were injected with fluorescently labeled HDL and particle uptake in the liver was analyzed using fluorescencemicroscopy. RESULTS: HDL uptake occurred via clathrin-coated pits, tubular endosomes and multivesicular bodies in human umbilical vein endothelial cells. During uptake and resecretion, HDL-derived cholesterol was exchanged at a faster rate than cholesteryl oleate, resembling the HDL particle pathway seen in hepatic cells. In addition, lysosomes were not involved in this process and thus HDL degradation was not detectable. In vivo, we found HDL mainly localized in mouse hepatic endothelial cells. HDL was not detected in parenchymal liver cells, indicating that lipid transfer from HDL to hepatocytes occurs primarily via scavenger receptor, class B, type Ⅰ mediated selective uptake without concomitant HDL endocytosis. CONCLUSION: HDL endocytosis occurs via clathrincoated pits, tubular endosomes and multivesicular bodies in human endothelial cells. Mouse endothelial cells showed a similar HDL uptake pattern in vivo indicating that the endothelium is one major site of HDL endocytosis and transcytosis.

A Modified Chitosan Adsorbent for Selective Removal of Low Density Lipoprotein

A modified chitosan adsorbent was synthesized through a simple preparation procedure, and it demonstrated good adsorption performance for selective removal of low density lipoprotein in human plasma. Phase inversion technique was employed to form chitosan beads, to which epoxy groups were then introduced by reacting with ethyleneglycol diglycidylether, and tryptophan was subsequently coupled to the epoxy-activated beads.

Effects of Oxidized Low Density Lipoprotein onthe Expression and Function of ABCA1 in Macrophages

Summary:In the present study, we examined the regulation of the expression and function of ABCA1 by modified LDL (ox-LDL) in vitro. After incubation with apoA-I for 24 h, RAW264.7 cells effluxed 37.65 % cholesterol loaded by acetyl LDL (ac-LDL), and 9.78 % cholesterol in ox-LDL group. The level of ABCA1 mRNA increased about three times either when cells were incubated with 100 μg /mL ac-LDL or with 100 μg /mL ox-LDL. However, the level of ABCA1 protein rose by 1.57 times in ac-LDL group and 1.26 times in ox-LDL group. These results demonstrated that ox-LDL had different effect on the expression and function of ABCA1, ox-LDL might decrease the cholesterol efflux mediated by ABCA1 through other unknown mechanisms.

Higher testosterone levels are associated with increased highdensity lipoprotein cholesterol in men with cardiovascular disease： results from the Massachusetts Male Aging Study

Aim： To study the relationship between circulating androgens （total testosterone [TT], free testosterone [IT] and dihydrotestosterone [DHT]） and high-density lipoprotein cholesterol （HDL-C） in men with and without cardiovascular disease （CVD）. Methods： Cross-sectional analyses included 1 661 baseline samples from the Massachusetts Male Aging Study （MMAS）, a population-based cohort of men ages 40-70 years. Serum hormones were measured by radioimmunoassay and HDL-C was determined following precipitation of the lower density lipoproteins. CVD was determined by self-report. Analyses were performed using multiple linear regression. Results： TT and HDL-C were positively correlated in the entire sample （r = 0.11, P = 0.0001）. After adjusting for confounders, we found this relationship was mostly limited to the 209 men with CVD. Among men with CVD, TT （P = 0.0004）, iT （P = 0.0172） and DHT （P = 0.0128） were all positively correlated with HDL-C, whereas in men without CVD only TT correlated with HDL-C （P = 0.0099）. Conclusion： Our results suggest that if androgens contribute to CVD in middle-aged men, the effect is not related to a suppressive effect of endogenous T on HDL-C. （Asian JAndrol 2008 Mar; 10： 193-200）

Lipoprotein in cholesterol transport: Highlights and recent insights into its structural basis and functional mechanism

Lipoproteins are protein-lipid macromolecular assemblies which are used to transport lipids in circulation and are key targets in cardiovascular disease （CVD）. The highly dynamic lipoprotein molecules are capable of adopting an array of conformations that is crucial to lipid transport along the cholesterol transport pathway, among which high-density lipopro- tein （HDL） and low-density lipoprotein （LDL） are major players in plasma cholesterol metabolism. For a more detailed illustration of cholesterol transport process, as well as the development of therapies to prevent CVD, here we review the functional mechanism and structural basis of lipoproteins in cholesterol transport, as well as their structural dynamics in the plasma lipoprotein （HDL and LDL） elevations, in order to obtain better quantitative understandings on structure-function relationship of lipoproteins. Finally, we also provide an approach for further research on the lipoprotein in cholesterol transport.

Inhibition of Oxidative Modification of Human Low Density Lipoprotein by Resveratrol

To further investigate whether resveratrol, a polyphenolic compound in red wine, affects the oxidation of human low density lipoprotein (LDL), LDL purified from normolipidemic subjects was subjected to Cu\+\{2+\}induced or azo compoundinitiated oxidative modification. The extent of LDL modification was assessed by measuring the formation of thiobarbituric acid reactive substances (TBARS) and the relative electrophoretic mobilities (REM) of LDL. Resveratrol (50 mol/L) reduced TBARS and REM of LDL during Cu\+\{2+\}induced oxidation by 70.5% and 42.3%, respectively (P<0.01), and prolonged the lag phase associated with the oxidative modification of LDL by copper ion or azo compound. These in vitro results suggest that resveratrol may afford LDL protection against oxidative modification, possibly by acting as a free radical scavenger.

Could Low Hdl-Cholesterol Levels Be an Unvalued Predictor of Cancer Risk?: A Retrospective Case Study

Background: The relationship between serum lipid profile levels and cancer risk remained uncertain. Recently, it had been reported a significant inverse association between high-density lipoprotein cholesterol (HDL) and the risk of incident cancer that was independent of low-density lipoprotein cholesterol (LDL), age or sex. Objective: The aim of our study was to evaluate the behavior of HDL in cancer patients and in healthy population. Methods: We created a retrospectively search strategy in the laboratory information system (LIS). We filtered and searched those patients with CEA within 5 - 20 ng/ml and any value of HDL and corroborated the presence of cancer (Group 1 (G1)) or not (Group 2 (G2)). Moreover, we searched a control group (patients in outpatient oncology clinic) to observe the values of HDL. Comparisons and statistical logistic regression models were applied to link the levels of this biomarkers and cancer risk. Results: We examined 852 valid patients, median age 62 (50 - 73) years. Within the search strategy group, G2 showed highest levels of HDL (54 (43 - 67) mg/dl) and lowest CEA levels (6.7 (5.7 - 8.4) ng/ml) comparing with G1: HDL (47 (37 - 60) mg/dl) and the CEA (7.9 (6.2 - 10.9) ng/ml);p p r2: 0.092;p p = 0.001)] and CEA [OR: 1.115 (1.060 - 1.174), (p < 0.001)] and they were confirmed as independent predictors of cancer. Conclusion: Our findings confirmed the inverse association of HDL levels between healthy populations and were diagnosed with cancer. Moreover, in a random population, patients with cancer presented lower HDL values compared to those without cancer. Therefore, it could demonstrate the possible positive predictive value of low HDL related to cancer risk.

The rate of patients at high risk for cardiovascular disease with an optimal low-density cholesterol level: a multicenter study from Thailand

Background Hypercholesterolemia is a major risk factor for cardiovascular events in patients with established atherosclerotic disease (EAD) and in those with multiple risk factors (MRFs). This study aimed to investigate the rate of optimal low-density lipoprotein (LDL) cholesterol level in a multicenter registry of patients at high risk for cardiovascular events. Methods A multicenter registry of EAD and MRF patients was conducted. Demographic data,medical history,cardiovascular risk factors,anthropometric data,laboratory data,and medications were recorded and analyzed. We classified patients according to target LDL levels based on recommendation by the European Society of Cardiology (ESC) 2011 into Group 1 which is EAD and diabetes or chronic kidney disease (CKD)–target LDL below 70 mg/dL,and Group 2 which is MRF without diabetes or CKD–target LDL below 100 mg/dL. The rate of optimal LDL level in patients with Group 1 and Group 2 was analyzed and stratified according to the treatment pattern of lipid-lowering medications. Results A total of 3100 patients were included. Of those,51.7% were male. Average age was 65.8 ± 9.7 years. Average LDL level was 96.3 ± 32.6 mg/dL. A vast majority (92.7%) received statin and 9.3% received ezetimibe. Optimal LDL level was achieved in 20.3% of patients in Group 1 (LDL < 70 mg/dL),and in 46.6% in Group 2 (LDL < 100 mg/dL). The overall rate of optimal LDL control was 23% since 89.6% of study population belongs to Group 1. The rate of optimal LDL was not different between high and low potency statin. Factors that were associated with optimal LDL control were older age,the presence of coronary artery disease or peripheral artery disease. Conclusions The rates of optimal LDL level were unacceptably low in this study population. As such,a strategy to improve LDL control in high-risk population should be implemented.

Regulation and deregulation of cholesterol homeostasis: The liver as a metabolic "power station"

Cholesterol plays several structural and metabolic roles that are vital for human biology. It spreads along the entire plasma membrane of the cell, modulating fluidity and concentrating in specialized sphingolipid-rich domains called rafts and caveolae. Cholesterol is also a substrate for steroid hormones. However, too much cholesterol can lead to pathological pictures such as atherosclerosis, which is a consequence of the accumu- lation of cholesterol into the cells of the artery wall. The liver is considered to be the metabolic power station of mammalians, where cholesterol homeostasis relies on an intricate network of cellular processes whose deregulations can lead to several life-threatening pathologies, such as familial and age-related hypercholesterolemia. Cholesterol homeostasis maintenance is carried out by: biosynthesis, via 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) activity; uptake, through low density lipoprotein receptors (LDLr); lipoprotein release in the blood; storage by esterification; and degradation and conversion into bile acids. Both HMGR and LDLr are transcribed as a function of cellular sterol amount by a family of transcription factors called sterol regulatory element binding proteins that are responsible for the maintenance of cholesterol homeostasis through an intricate mechanism of regulation. Cholesterol obtained by hepatic de novo synthesis can be esterified and incorporated into apolipoprotein B-100-containing very low density lipoproteins, which are then secreted into the bloodstream for transport to peripheral tissues. Moreover, dietary cholesterol is transferred from the intestine to the liver by high density lipoproteins (HDLs); all HDL particles are internalized in the liver, interacting with the hepatic scavenger receptor (SR-B1). Here we provide an updated overview of liver cholesterol metabolism regulation and deregulation and the causes of cholesterol metabolism-related diseases. Moreover, current pharmacological treatment and novel hypocho-lesterolemic strategies will also be introduced.

Triglycerides and ratio of triglycerides to high-density lipoprotein cholesterol are better than liver enzymes to identify insulin resistance in urban middle-aged and older non-obese Chinese without diabetes

Background Insulin resistance （IR） plays an important pathophysiological role in the development of diabetes,dyslipidemia,hypertension,and cardiovascular disease.Moreover,IR can occur even in non-obese people without diabetes.However,direct detection of IR is complicated.In order to find a simple surrogate marker of IR early in nonobese people,we investigate the association of commonly-used biochemical markers （liver enzymes and lipid profiles） with IR in urban middle-aged and older non-obese Chinese without diabetes.Methods This cross-sectional study included 1 987 subjects （1 473 women）.Fasting blood samples were collected for measurement of glucose,insulin,liver enzymes,lipid profiles and creatinine.Subjects whose homeostasis model of assessment-IR （HOMA-IR） index values exceeded the 75th percentile （2.67 for women and 2.48 for men） of the population were considered to have IR.The area under the receiver operating characteristic curve （ROC） was used to compare the power of potential markers in identifying IR.Results Triglycerides （TG） and ratio of TG to high-density lipoprotein cholesterol （TG/HDL-C） discriminated IR better than other indexes for both sexes; areas under the receiver operating characteristic （ROC） curves （AUC） values were 0.770 （95％ confidence interval 0.733-0.807） and 0.772 （0.736-0.809）,respectively,for women and 0.754 （0.664-0.844）and 0.756 （0.672-0.840）,respectively,for men.To identify IR,the optimal cut-offs for TG and TG/HDL-C ratio were 1.315 mmol/L （sensitivity 74.3％,specificity 71.0％） and 0.873 （sensitivity 70.1％,specificity 73.4％）,respectively,for women,and 1.275 mmol/L （sensitivity 66.7％,specificity 74.4％） and 0.812 （sensitivity 75.8％,specificity 69.2％）,respectively,for men.Conclusion TG and TG/HDL-C ratio could be used to identify IR in urban middle-aged and older non-obese Chinese without diabetes.

Apolipoprotein A1,the neglected relative of Apolipoprotein E and its potential role in Alzheimer’s disease

Lipoproteins are multi-molecule assemblies with the primary function of transportation and processing of lipophilic substances within aqueous bodily fluids(blood,cerebrospinal fluid).Nevertheless,they also exert other physiological functions such as immune regulation.In particular,neurons are both sensitive to uncontrolled responses of the immune system and highly dependent on a controlled and sufficient supply of lipids.For this reason,the role of certain lipoproteins and their protein-component(apolipoproteins,Apo’s)in neurological diseases is perceivable.ApoE,for example,is well-accepted as one of the major risk factors for sporadic Alzheimer’s disease with a protective allele variant(ε2)and a risk-causing allele variant(ε4).ApoA1,the major protein component of high-density lipoproteins,is responsible for transportation of excess cholesterol from peripheral tissues to the liver.The protein is synthesized in the liver and intestine but also can enter the brain via the choroid plexus and thereby might have an impact on brain lipid homeostasis.This review focuses on the role of ApoA1 in Alzheimer’s disease and discusses whether its role within this neurodegenerative disorder is specific or represents a general neuroprotective mechanism.

Predictive and Prognostic Value of High-density Lipoprotein Cholesterol in Young Male Patients with Acute Myocardial Infarction

Background： The level of high-density lipoprotein cholesterol （HDL-C） is an important risk indicator and used in risk factor counting and quantitative risk assessment; however, the effect of HDL-C in young male patients with acute myocardial infarction （AMI） is unclear. The aim of this study was to investigate the effect of HDL-C in young male patients. Methods： We recruited 267 consecutive young male patients （≤44 years） diagnosed with AMI. Other 247 participants free from coronary heart disease were enrolled as controls. HDL-C levels of AMI patients and controls were evaluated to analyze the predictive value on AMI. According to the cutoff point of 1.04 mmol/L HDL-C, patients of AMI were divided into two subgroups （normal HDL-C group and low HDL-C group） and were followed up for 2 years. Clinical end points included all major adverse coronary events （MACEs）： the main cause of death, nonfatal myocardial infarction, readmissions for acute coronary syndrome, arrhythmias, or revascularization. The prognostic value of HDL-C was evaluated using Cox regression according to MACE. Results： Patients of AMI had decreased proportion in normal HDL-C group compared to controls （47.2% vs. 57.9%; P = 0.017）. Logistic regression analysis showed that there was an inverse relationship between HDL-C and AMI in young males. In the low HDL-C subgroup of AMI patients （n = 141）, 34 （24.1%） patients experienced a MACE during the 2-year follow-up, compared with 15 （11.9%） patients in normal HDL-C subgroup （n = 126）. The Cox regression analysis showed that HDL-C was an independent predictor of a MACE during the follow-up period （hazard ratio = 0.354, P = 0.006）. Conclusion： HDL-C was an important parameter for predicting the risk and the clinical outcomes of AMI in young male patients.