High Density Lipoprotein Phospholipids as a Marker of Coronary Heart Disease of Shen-Yang Deficiency Syndrome

Objective: To seek a new biochemical index for diagnosis of coronary heart disease (CHD) of shen-Yang deficiency syndrom (CHD-SYD). Methods: Sixty-one patients with CHD were divided into 3 groups according to their TCM Syndrome type, 10 patients in the group without Xin-Qi deficiency (Group A), 25 in the group with Xin-Qi deficiency but without Shen-Yang deficiency (Group B) and 26 in the group both with Xin-Qi deficiency and Shen-Yang deficiency (Group C). Levels of 17-hydroxy-corticoste-roid in urine (urinary 17-OHCS) per 24 hrs, and serum level of high density lipoprotein cholesterol (HDL-C) and high density lipoprotein phospholipid (HDL-PL) in them were determined in synchrostep and compared with those in the control group of 23 healthy aged persons, urinary 17-OHCS per 24 hrs was taken as the diagnostic standard to screen a new index for diagnosis of Shen-Yang deficiency Syndrome, and preliminary appraisal to the index was made. Results: Serum HDL-PL in the CHD-SYD patients( Group C) was 616+157 mg/L, which was obviously lower than that in the patients of Group A and B. With low HDL-PL(<650 mg/L) used as the index to diagnose CHD-SYD, the sensitivity was 73%, the specificity 86% and the accuracy 80%. Conclusion: HDL-PL <650 mg/L could be adopted as an index for CHD-SYD diagnosis, which is simple and practical.

SNP Detection of High Density Lipoprotein Binding Protein Gene (HBP) and Its Correlations with Growth Traits in Largemouth Bass(Micropterus salmoides)

High density lipoprotein binding protein （HBP） plays an important role in lipid metabolism of animals. Lipids are indispensable energy materials for fi- shes, especially for carnivorous fishes with low utilization efficiency of carbohydrates. The single nucleotide polymorphism （SNP） of HBP gene may affect the fat metabolism, thereby exerting an effect on the growth traits of largemouth bass （Micropterus salmoides）. Investigating the correlations between SNP and growth traits can provide candidate markers for molecular marker-assisted selection. In this study, partial genomic fraganents of HBP gene （ GenBank accession number： KF652241 ） were amplified based on the sequences of an available contig in the EST-SNP database of largemouth bass. Three SNP mutation loci were identified in the 3＇ non-ceding region of HBP gene by direct sequencing, including H1 （G ＋ 2782T）, 142 （T ＋ 2817C） and H3 （G ＋ 2857A）. Three SNP loci of 165 randomly selected largemouth bass individuals were detected and genotyped by SnaPshot assay. Genetic structure was analyzed by POPGENE32 software. By using spssl7.0 software, a general linear model （GLM） was established for correlation analysis between different genotypes at SNP loci of HBP gene and various growth traits. The results showed that three SNP loci were in Hardy-Weinberg equilibrium state. To be specific, loci H1 and H2 formed two haplotypes （ A and B）, and three geno- types （AA, AB, and BB） were observed; loci H1, H2 and H3 formed six diplotypes （DI, I）2, D3, D4, D5 and D6）. According to the correlations between dif- ferent genotypes and various growth traits, the body weight and total length of largemouth bass individuals with genotype BB were significantly higher than those of individuals with genotype AB （ P 〈 0.05 ） ; the body weight and total length of largemouth bass individuals with diplotype D6 were significantly higher than those of individuals with diplotype D4 （P 〈0.05）. In this study, SNP markers correlated with growth traits were obtained in the 3＇ non-coding region ofHBP gene in large-mouth bass, which could be used as candidate genetic markers for subsequent molecular marker-assisted selection breeding of largemouth bass.

The pleiotropic vasoprotective functions of high density lipoproteins(HDL)

The pleiotropic functions of circulating high density lipoprotein（HDL） on peripheral vascular health are well established. HDL plays a pivotal role in reverse cholesterol transport and is also known to suppress inflammation,endothelial activation and apoptosis in peripheral vessels. Although not expressed in the central nervous system, HDL has nevertheless emerged as a potential resilience factor for dementia in multiple epidemiological studies. Animal model data specifically support a role for HDL in attenuating the accumulation of P-amyloid within cerebral vessels concomitant with reduced neuroinflammation and improved cognitive performance. As the vascular contributions to dementia are increasingly appreciated, this review seeks to summarize recent literature focused on the vasoprotective properties of HDL that may extend to cerebral vessels, discuss potential roles of HDL in dementia relative to brainderived lipoproteins, identify gaps in current knowledge, and highlight new opportunities for research and discovery.

Research progress of monocyte/high density lipoprotein ratio in cardiovascular diseases

In recent years,monocyte to high density lipoprotein cholesterol ratio(MHR)has attracted wide attention as a new marker of inflammatory response.This indicator includes two aspects:inflammatory response and lipid accumulation,which are the two most basic characteristics of Atherosclerosis(AS).AS is closely related to the occurrence of Cardiovascular diseases(CVD).A large number of existing studies have confirmed that MHR is an inflammatory marker that can dynamically reflect the trend of inflammation,can reflect the chronic inflammatory response in blood vessels,and can evaluate the occurrence,development and prognosis of cardiovascular disease in a non-invasive manner.This article reviews recent studies on the role of monocytes and high-density lipoproteins in chronic inflammation of blood vessels,as well as the current status of research on MHR and cardiovascular disease in the light of recent literature.

Apparent protective effect of high density lipoprotein against coronary heart disease in the elderly

Background This study was designed to evaluate the relationship between high-density lipoprotein cholesterol (HDL-C) level and acute myocardial infarction (AMI) and coronary heart disease (CHD) death and to explore the protective effect of HDL against CHD in the elderly Chinese.Methods Started from 1986, 1211 retirees (92% males) were enrolled consecutively and studied prospectively. The average starting age was 70±9 years, and that at the end of the study was 80±9 years. During the follow-up study, all the participants received yearly physical examination and blood chemistry survey from 1986-2000. The average duration of the follow up study was 11.2 years. The end point of this study was either attacks of AMI or death due to CHD and other causes. CHD risk factors were screened by logistic regression analysis. According to their HDL-C levels, cases were divided into low (<1.03 mmol/L), medium (or normal, 1.03-1.56 mmol/L) and high (>1.56 mmol/L) level groups, the differences in incidence of AMI and CHD death in each group were analyzed.Results The cumulative attacks of acute coronary syndrome (mostly AMI) were 214 cases, including 89 cases of coronary death and 308 death caused by other diseases during the follow up study. AMI occurrence and CHD death in normal HDL-C group were lower than those in the low HDL-C group by 40% and 53%; and those in the high HDL-C group were lower than in the normal group by 56% and 50%, respectively. Statistical analysis on normal lipid cases (411 cases, total cholesterol<5.17mmol/L, triglyceride<1.69 mmol/L) revealed that the cases at low HDL-C level had similar rates of AMI events and CHD mortality as those of the entire group (including hyperlipidemia); however, AMI attacks and CHD deaths decreased significantly at the normal and high HDL-C levels. The results demonstrated that the protective effect of HDL against coronary artery disease is more prominent in people with low lipid level.Conclusion Low HDL is an important independent risk factor for AMI attacks and CHD death in the elderly; high HDL has significant protective effect against coronary artery disease.

Study on the Relationship between Serum High Density Lipoprotein and Pi-deficiency Syndrome in Patients with Coronary Heart Disease

Objective： To explore the relationship of Pi （脾）-deficiency syndrome in TCM with the change of serum high density lipoprotein （HDL） in blood lipid metabolic disorder. Methods： Sixty-eight patients with confirmed coronary heart disease （CHD） were selected for TCM syndrome typing into Pi- deficiency （PD） group and non-Pi-deficiency （NPD） group. Routine blood lipids and serum lipoprotein electrophoretogram （SLPG） were determined in all patients to analyze the total content of HDL and its relative contents of sub-components HDL1-5, as well as their relation with PD syndrome. Besides, a healthy control group （62 cases） was set up. Results： The level of serum HDL-C was lowered, SLPG abnormality rate increased in the patients with CHD, with total HDL and the relative contents of sub- component HDL1 and HDL3 significantly lower than those in the healthy control group （P〈0.01）. The total HDL, HDL1 and HDL3 in the PD group were also lower than those in the NPD group （P〈0.05, P〈0.01）. Conclusion： Serum HDL and its sub-components showed a definite relation with TCM PD syndrome type, therefore, further exploring the granular specificity of HDL and its sub-components as well as their influence on reverse cholesterol transport （RCT） may hopefully provide clues for developing RCT regulatory Chinese new drugs and for CHD prevention and treatment.

Expression of human hepatic lipase negatively impacts apolipoprotein A-Ⅰ production in primary hepatocytes from Lipc-null mice

This study aimed to examine whether expression of human hepatic lipase（hHL） exerted an intracellular effect on hepatic production of apolipoprotein（apo） A-I.The levels of secreted and cell-associated apoA-I were contrasted between primary hepatocytes isolated from Lipc-nuW and C57BL/6 mice,and between Lipc-nuW hepatocytes transfected with either hHL-encoding or control adenovirus.An HSPG-binding deficient hHL protein（hHLmt） was used to determine the impact of cell surface binding on HL action.Accumulation of apoA-I in conditioned media of primary hepatocytes isolated from Lipc-nuW mice was increased as compared to that from C57BL/6 mice.Metabolic labeling experiments showed that secretion of ＇＇S-apoA-I from Lipc-nuW cells was significantly higher than that from C57BL/6 cells.Expression of hHL in Lipc-nuW hepatocytes,through adenovirus-mediated gene transfer,resulted in decreased synthesis and secretion of ＇S-apoA-I,but not S-apoE,as compared with cells transfected with control adenovirus.Expression of HSPG-binding deficient hHLmt in Lipc-nuW cells also exerted an inhibitory effect on apoA-I production,even though hHLmt displayed impaired exit from the endoplasmic reticulum as compared with hHL.Subcellular fractionation revealed that expression of hHL or hHLmt led to increased microsome-association of apoA-I relative to non-transfected control.Expression of hHL negatively impacts hepatic production of apoA-I.

Apolipoprotein B Is a Good Tool for Screening Dyslipidaemia in Apparently Healthy Population

Dyslipidaemia is the major risk factor for cardiovascular disease (CVD) which is the leading cause of death in the world. Even though several lipid parameters are used, currently apolipoprotein B (apoB) is considered as the best predictor of CVD. Thus this study was carried out to find out the association between conventional lipid parameters and apoB in apparently healthy subjects. A descriptive cross-sectional study was carried out in 170 apparently healthy volunteers who were not diagnosed with dyslipidaemia. After 12 hours overnight fast venous blood was obtained and Total cholesterol (TC), Triglyceride (TG), High density lipoprotein cholesterol (HDL-C) were measured by enzymatic kit method. Low density lipoprotein cholesterol (LDL-C) was calculated by Friedewald formula and apoB was analyzed by immune turbid metry using a Konelab® auto analyzer. Among the participants, majority (63.5%) were females. The mean value of apoB concentration of the population was 103 ± 42 mg/dL which was similar and not significantly different between the genders (Males, 102 ± 37 mg/dL and Females, 104 ± 45 mg/dL). All lipid parameters showed a positive correlation with apoB concentration whereas HDL-C had a negative correlation (r = -0.165). HDL-C significantly (p < 0.05) decreased with increase in apoB concentration while LDL-C, TC/HDL-C and non-HDL-C significantly (p < 0.05) increased with an increase in apoB concentration. Present study suggests that serum apoB has better correlations and associations with the parameters that are used in conventional lipid profile and with markers recommended for diagnosing dyslipidaemia. Hence apoB could be used as a single marker for screening dyslipidaemia in apparently healthy people.

Protective Effects of Xiongshao Capsule(芎芍胶囊) on Anti-inflammatory Function of High-Density Lipoprotein in AnAtherosclerosis Rabbit Model

Objective： To observe the effects of Xiongshao Capsule（芎芍胶囊, XSC） on anti-inflammatory properties of high-density lipoprotein（HDL）, myeloperoxidase（MPO） and paraoxonase 1（PON1） in serum of atherosclerosis（AS） rabbit model and explore the anti-inflammatory protective effects of XSC on HDL. Methods： Sixty rabbits were randomized into the control, the model, XSC low-, medium-and high-dose（Rhizoma Chuanxiong ＋ Radix Paeoniae rubra ： 0.6＋0.3, 1.2＋0.6, 2.4＋1.2 g·kg-1·day-1, respectively）, and simvastatin（1 g·kg-1·day-1） groups. The model rabbits were fed with high-fat diet and respective drugs for 15 weeks. The blood and thoracic aortas samples were collected at the end of 15 weeks. The levels of serum MPO and PON1 as well as total cholesterol（TC） and free cholesterol（FC） in aorta wall cells were tested by enzyme linked immunosorbent assay. Results： TC and FC in the model group were significantly higher than those in the control group（P〈0.01）. Compared with the model group, TC and FC in the XSC groups were significantly lower（P〈0.05 or P〈0.01）, so was simvastatin group（P〈0.01）. There was no significant difference in PON1 level between groups（P〉0.05）, even between model and control groups（P〉0.05）. The serum MPO level in the model group was significantly higher than that in the control group（P〈0.05）, which was significantly lower in XSC groups as well as simvastatin group（P〈0.05 or P〈0.01）, and no difference was found between XSC groups and simvastatin group（P〉0.05）. Conclusions： XSC can reduce the serum MPO level in AS rabbits to protect the anti-inflammatory function of HDL, maintaining the normal lipid transport function. TC and FC levels in aorta cells decline, and this process initiated by XSC plays an anti-AS role.

The shape effect of reconstituted high-density lipoprotein nanocarriers on brain delivery and Aβ clearance

Accumulation of extracellular β-amyloid （Aβ） is crucial for the pathogenesis of Alzheimer＇s disease （AD）, and the development of novel therapeutic agents that can both accelerate Aβ clearance and inhibit the subsequent pathological cascades is regarded as a promising strategy for AD management. In our previous study, we have constructed discoidal apolipoprotein E3-reconstituted high-density lipoprotein （ApoE3-rHDL） as an efficient nanoplatform that can penetrate the blood-brain barrier and accelerate Aβ clearance for a combination treatment of AD. To further improve its drug loading capacity, we hypothesized that spherical rHDL might serve as a more powerful nanocarrier if it has the same brain delivery and Aβ clearance abilities as the discoidal rHDL does. To evaluate the potential of spherical rHDL as a promising alternative for the combination therapy for AD, here, we investigated the effect of the shape of rHDL on its brain delivery, Aβ clearance, and anti-AD efficacy. We found that spherical rHDL had stronger Aβ-binding affinity than discoidal rHDL did, more effectively facilitated microglial uptake and degradation of Aβ-42, achieved better brain distribution after intravenous administration, and more powerfully reduced Aβ deposition, decreased microglia activation, attenuated neurological damage, and rescued memory deficits in a mouse model of AD. Among the rHDLs evaluated, monosialotetrahexosyl ganglioside-incorporated spherical rHDL exerted the best effect. The findings of this study for the first time show a shape effect of an rHDL nanocarrier on its biological functions and suggest that a spherical lipoprotein-mimic nanocarrier may serve as a more efficient multifunctional nanoplatforrn for AD therapy.

Blood Lipid Profile and Prevalence of Dyslipidemia in Chinese Adults

To investigate the plasma lipid levels in a national representative sample of subjects and to determine the prevalence of dyslipidemia in the Chinese population. Methods Plasma lipid profile was analyzed using the data obtained during the Chinese national nutrition and health survey （CNHS） in 2002 which involved 14 252 participants at the age of 18 years or older. Results The mean levels of total cholesterol （TC）, triglyceride （TG） and high density lipoprotein cholesterol （HDL-C） in the participants were 3.81 retool/L, 1.10 mmol/L, and 1.30 mmol/L, respectively. In the groups of participants at the age of 18-44 years, 45-59 years, and over 60 years the mean TC level was 3.70 mmol/L, 4.09 mmol/L and 4.21 mmol/L, respectively, and the mean TG level was 07 mmol/L, 1.21 mmol/L, 1.20 mmol/L, 1.29 mmol/L, 1.33 mmol/L, and 1.33 mmol/L, respectively. The prevalence of dyslipidemia in Chinese adults was 18.6% and 22.2% in males and 15.9% in females. Dyslipidemia prevalence was higher in urban districts than in rural areas （21.0% vs. 17.7%）. The prevalence of hypercholesterolemia, hypertriglyceridemia, and low HDL cholesterol was 2.9%, 11.9%, and 7.4% respectively among the participants. Conclusion Dyslipidemia has become one of the important health risk factors in the Chinese population. There is no significantly difference in the prevalence of dyslipidemia between the groups of participants at the age of 45-59 years and over 60 years. This study provides important lipid profile data for policy making and guideline development for the prevention of dyslipidemia in the Chinese population.

Association of serum lipid levels with diabetic retinopathy

AIM: To assess the association between serum lipids and diabetic retinopathy (DR). · METHODS: Sixty -one diabetic patients without retinopathy (NDR), 55 diabetic patients with non - proliferative retinopathy (NPDR) and 75 diabetic patients with proliferative retinopathy (PDR) according to ETDRS grading scale were enrolled in this study. Total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL) and triglyceride values were compared between the groups. ·RESULTS: The groups were well-balanced in terms of age and gender (P =0.071, P =0.265 respectively). The mean HbA1c values were significantly lower in NDR group than the NPDR and PDR groups(P =0.004, P =0.009 respectively). Mean total cholesterol, triglyceride, LDL, HDL and VLDL levels were not significantly different between the groups (P =0.693, P =0.774, P =0.644, P = 0.910 and P =0.967 respectively, one way ANOVA). Mean total cholesterol, triglyceride, LDL, HDL and VLDL levels were not significantly different between the patients with ME and patients without ME(P =0.622, P =0.113, P =0.955, P =0.735 and P =0.490 respectively, t -test). The mean blood glucose significantly correlated with total cholesterol (r =0.173, P =0.017) and LDL (r =0.190, P = 0.008). The mean HbA1c significantly correlated with total cholesterol (r =0.158, P =0.030) and triglyceride (r =0.148, P =0.042). ·CONCLUSION: Serum lipid levels were not significantly associated with the severity of DR or existence of ME despite the significant correlation between the mean blood glucose, HbA1c and total cholesterol.

Biliary cholesterol secretion: More than a simple ABC

Biliary cholesterol secretion is a process important for 2 major disease complexes, atherosclerotic cardiovascular disease and cholesterol gallstone disease. With respect to cardiovascular disease, biliary cholesterol secretion is regarded as the f inal step for the elimination of cholesterol originating from cholesterol-laden macrophage foam cells in the vessel wall in a pathway named reverse cholesterol transport. On the other hand, cholesterol hypersecretion into the bile is considered the main pathophysiological determinant of cholesterol gallstone formation. This review summarizes current knowledge on the origins of cholesterol secreted into the bile as well as the relevant processes and transporters involved. Next to the established ATP-binding cassette (ABC) transporters mediating the biliary secretion of bile acids (ABCB11), phospholipids (ABCB4) and cholesterol (ABCG5/G8), special attention is given to emerging proteins that modulate or mediate biliary cholesterol secretion. In this regard, the potential impact of the phosphatidylserine flippase ATPase class Ⅰ type 8B member 1, the Niemann Pick C1-like protein 1 that mediatescholesterol absorption and the high density lipoprotein cholesterol uptake receptor, scavenger receptor class B type Ⅰ, is discussed.

Serum parameters predict the severity of ultrasonographic findings in non-alcoholic fatty liver disease

BACKGROUND: Controversy exists about the correlation between liver ultrasonography and serum parameters for evaluating the severity of liver involvement in non-alcoholic fatty liver disease (NAFLD). This study was designed to determine the association between liver ultrasonography staging in NAFLD and serum parameters correlated with disease severity in previous studies; and set optimal cut-off points for those serum parameters correlated with NAFLD staging at ultrasonography, in order to differentiate ultrasonographic groups (USGs). METHODS: This cross-sectional study evaluated outpatients with evidence of NAFLD in ultrasonography referred to a general hospital. Those with positive viral markers, abnormal serum ceruloplasmin or gamma-globulin concentrations were excluded. A radiologist performed the ultrasonography staging and stratified the patients into mild, moderate, and severe groups. Fasting serum alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase, triglyceride (TG), high and low density lipoprotein (HDL, LDL), and cholesterol were checked. RESULTS: Two hundred and forty-five patients with a mean age (±standard deviation) of 41.63(±11.46) years were included. There were no significant differences when mean laboratory concentrations were compared between moderate and severe USGs. Therefore, these groups were combined to create revised USGs ('mild' versus 'moderate or severe'). There were associations between the revised USGs, and ALT, TG, HDL levels, and diabetes mellitus [odds ratios=2.81 (95% confidence interval (CI): 1.37-5.76), 2.48 (95% CI: 1.29- 4.78), 0.36 (95% CI: 0.18-0.74), and 5.65 (95% CI: 2.86-11.16)respectively; all P values <0.01]. A cut-off value of 32.5 mg/dL for ALT gave a sensitivity of 70% and a specificity of 62%, for differentiating between the revised USGs. CONCLUSIONS: Serum ALT, TG, and HDL concentrations seem to be associated with the staging by liver ultrasonography in NAFLD. They might be used to predict the staging of liver ultrasonography in these patients.

Association of serum lipids and severity of epithelial ovarian cancer：an observational cohort study of 349 Chinese patients

While obesity and fat intake have been associated with the risk and prognosis of epithelial ovarian cancer, the association between the lipid levels and epithelial ovarian cancer phenotype remains controversial. We conducted a retrospective study of 349 epithelial ovarian cancer patients who received treatment at Jiangsu Cancer Hospital, China between 2011 and 2017. We analyzed age at diagnosis, blood pressure, plasma glucose content, body mass index（BMI）, lipid levels and clinical parameters. Severity of epithelial ovarian cancer was classified according to the International Federation of Gynecology and Obstetrics（FIGO） grading system. Univariate analysis of the clinical factors according to the severity of epithelial ovarian cancer was followed by logistic regression analysis to identify clinical factors significantly associated with epithelial ovarian cancer severity. Univariate analysis indicated that age,BMI, triglyceride（TG）, and high density lipoproteins（HDL） differed significantly among different stages of epithelial ovarian cancer（P〈0.05）. In the logistic regression model, elevated TG（OR： 1.883; 95% CI= 1.207-2.937）, and low HDL（OR： 0.497; 95% CI = 0.298-0.829） levels were significantly associated with the high severity epithelial ovarian cancer. Our data indicate that high TG and low HDL levels correlate with a high severity of epithelial ovarian cancer. These data provide important insight into the potential relationship between the lipid pathway and epithelial ovarian cancer phenotype and development.

HDL signaling and protection against coronary artery atherosclerosis in mice

Atherosclerosis is a leading underlying factor in cardiovascular disease and stroke,important causes of morbidity and mortality across the globe.Abundant epidemiological studies demonstrate that high levels of high density lipoprotein（HDL） are associated with reduced risk of atherosclerosis and preclinical,animal model studies demonstrate that this association is causative.Understanding the molecular mechanisms underlying the protective effects of HDL will allow more strategic approaches to development of HDL based therapeutics.Recent evidence suggests that an important aspect of the ability of HDL to protect against atherosclerosis is its ability to trigger signaling responses in a variety of target cells including endothelial cells and macrophages in the vessel wall.These signaling responses require the HDL receptor,scavenger receptor class B type 1（SR-B1）,an adaptor protein（PDZK1） that binds to the cytosolic C terminus of SR-B1,Akt1 activation and（at least in endothelial cells） activation of endothelial NO synthase（eNOS）.Mouse models of atherosclerosis,exemplified by apolipoprotein E or low density lipoprotein receptor gene inactivated mice（apoE or LDLR KO） develop atherosclerosis in their aortas but appear generally resistant to coronary artery atherosclerosis.On the other hand,inactivation of each of the components of HDL signaling（above）in either apoE or LDLR KO mice renders them susceptible to extensive coronary artery atherosclerosis suggesting that HDL signaling may play an important role in protection against coronary artery disease.

Ecto-F_1-ATPase: A moonlighting protein complex and an unexpected apoA-I receptor

Mitochondrial ATP synthase has been recently detected at the surface of different cell types, where it is a high affinity receptor for apoA-I, the major protein component in high density lipoproteins (HDL). Cell surface ATP synthase (namely ecto-F1-ATPase) expression is related to different biological effects, such as regulation of HDL uptake by hepatocytes, endothelial cell proliferation or antitumor activity of Vγ9/Vδ2 T lymphocytes. This paper reviews the recently discovered functions and regulations of ecto-F1-ATPase. Particularly, the role of the F1-ATPase pathway(s) in HDL-cholesterol uptake and apoA-Imediated endothelial protection suggests its potential importance in reverse cholesterol transport and its regulation might represent a potential therapeutic target for HDL-related therapy for cardiovascular diseases. Therefore, it is timely for us to better understand how this ecto-enzyme and downstream pathways are regulated and to develop pharmacologic interventions.

The distribution and cell uptake of ApoA1 modified lipid carriers of siRNA in mouse liver in vivo

Fluorescence labeled small interfering RNAs(siRNAs)were loaded into lipopolyplexes modified with ApoA1(named as rHDL)and administered by intravenous injection.The biodistribution with time of these lipopolyplexes inside the liver and among various cell types was followed using tissue sections by Confocal fluorescence microscopy.At about 0.5 h after tail vein injection at a dose of 0.408 mg/kg,very few fluorescence signals were found in the liver.But then the signals could be seen to accumulate inside hepatocytes as discrete spots and diffused signals at around 2e4 h after injection.Such a distribution and uptake pattern was significantly different from what were observed using the commercial agent Invivofectamine
2.0 or DOTAP lipoplexes as the carriers.The differences indicated different mechanisms concerning the in vivo behavior of these carriers.The rHDL carrier system we developed was able to deliver siRNA specifically into hepatocytes while avoiding the uptake by REM cells especially the Kupffer cells.With it’s low toxicity and off target effect,it may be suitable to be developed as a hepatocyte targeting delivery system for siRNA.

Diagnostic Value of NPAR,MHR,GLU and Coronary Heart Disease Complicated with Type 2 Diabetes Mellitus

[Objectives]To explore the relationship between neutrophil percentage to albumin ratio(NPAR),monocyte to high density lipoprotein ratio(MHR),fasting blood glucose(GLU)and CAD+T2DM and its diagnostic value.[Methods]A total of 3937 patients who underwent coronary angiography in the Affiliated Hospital of Chengde Medical University from January 2016 to December 2018 were collected.The patients with Gensini score>0 and diabetes were selected as the experimental group(CAD+T2DM,n=756),and the patients with Gensini score=0 and without diabetes were taken as the control group(n=388),with a total of 1144 cases.The patient's medical record number,sex,age,contact number,biochemical test results,cardiac color ultrasound,coronary artery imaging and other data were recorded.NPAR,MHR,and GLU were calculated.A binary Logistic regression model was established combined with the receiver operating characteristic(ROC)curve.The predictive value of single index and joint test for CAD+T2DM was analyzed.[Results]The serum levels of NPAR,MHR and GLU in CAD+T2DM were significantly higher than those in the control group.Binary Logistic regression analysis showed that serum NPAR,MHR and GLU were risk factors for CAD+T2DM(P<0.05).The final prediction model is P=1/[1+e-(-3.722+0.014×NPAR+0.51×MHR+0.461×GLU)].ROC curve showed that the area under the curve of serum NPAR,MHR and GLU was 0.739,0.628 and 0.852,respectively,and the prediction probability of combined detection was 0.882,which was significantly higher than that of single index.[Conclusions]There was a close correlation between serum NPAR,MHR,GLU and CAD+T2DM in patients with coronary heart disease.The combined application of these indexes can significantly improve the predictive value of CAD+T2DM.

Effect of HDL and apo AI on PGE_2 Production by Monocyte-Derived Macrophages

Effect of antiatherogenic high density lipoprotein (HDL) and apolipoprotein AI (apo AI) on production of prostaglandin E2 (PGE2 ) by human m onocyte- derived macrophages was investigated.Macrophages were loaded with acetylated low density lipoprotein followed by incuba- tion with HDL3or apo AI.PGE2 produced and secreted in culture supernatant was quantified by en- zyme im munoassay.HDL3induced production of PGE2 by m acrophages in a time- dependent m an- ner.2 4 h after incubation,PGE2 production by HDL3- treated macrophages increased 3.7- fold of that by control cells.Apo AI also induced PGE2 secretion to 2 .1- fold,which was significantly less than HDL3.The data indicate that both HDL3and lipid- free apo AI enhance PGE2 synthesis and se- cretion by hum an m acrophages and this may further contribute to the protection from atheroscle- rosis.