LDL-C Concentrations Research Articles

Effect and mechanism of high-fat diet on the preference for sweeteners on mice.

Male Kunming mice were divided into a normal diet group (control group) and a high-fat diet group (HF group) (185 g·kg-1 protein, 600 g·kg-1 fat and 205 g·kg-1 carbohydrate). After 8 weeks' feeding, behavioral indicators and biochemical indicators in serum were determined. The double-bottle preference experiment was used to study the preferences of mice for five sweeteners. The monoamine neurotransmitter content, gene expression related to dopamine (DA), and opioid receptors were also determined. The body weight of the mice in the HF group increased significantly (P < 0.05) after 36 days compared with the control group. The feed intake of the HF group increased sharply in the first 12 days, and then it became basically unchanged. The preference of the HF group for all of the five sweeteners was highly significantly lower (P < 0.01) than that of the control group. Depression-related behavior was observed in the HF group mice. The triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDLC) content in the HF group were very much higher (P < 0.01) than those of the control group. The gene expression related to DA and opioid receptor in the HF group was significantly lower than that of the control group, except for preproenkephalin (PENK). In summary, this study suggested that a long-term high-fat diet could result in a decrease in the preference for sweeteners and could result in a state of reward hypofunction in mice. © 2020 Society of Chemical Industry.

Measuring the contribution of Lp(a) cholesterol towards LDL-C interpretation

BackgroundLipoprotein(a) [Lp(a)] is a pro-atherogenic and pro-thrombotic LDL-like particle recognized as an independent risk factor for cardiovascular disease (CVD). The cholesterol within Lp(a) (Lp(a)-C) contributes to the reported LDL-cholesterol (LDL-C) concentration by nearly all available methods. Accurate LDL-C measurements are critical for identification of genetic dyslipidemias such as familial hypercholesterolemia (FH). FH diagnostic criteria, such as the Dutch Lipid Clinic Network (DLCN) criteria, utilize LDL-C concentration cut-offs to assess the likelihood of FH. Therefore, failure to adjust for Lp(a)-C can impact accurate FH diagnosis and classification, appropriate follow-up testing and treatments, and interpretation of cholesterol-lowering treatment efficacy. ObjectiveIn this study, we use direct Lp(a)-C measurements to assess the potential misclassification of FH from contributions of Lp(a)-C to reported LDL-C in patient samples submitted for advanced lipoprotein profiling. MethodsA total of 31,215 samples submitted for lipoprotein profiling were included. LDL-C was measured by beta quantification or calculated by one of three equations. Lp(a)-C was measured by quantitative lipoprotein electrophoresis. DLCN LDL-C cut-offs were applied to LDL-C results before and after accounting for Lp(a)-C contribution. ResultsLp(a)-C was detected in 8665 (28%) samples. A total of 940 subjects were reclassified to a lower DLCN LDL-C categories; this represents 3% of the total patient series or 11% of subjects with measurable Lp(a)-C. ConclusionLp(a)-C is present in a significant portion of samples submitted for advanced lipid testing and could cause patient misclassification when using FH diagnostic criteria. These misclassifications could trigger inappropriate follow-up, treatment, and cascade testing for suspected FH.

Urinary copper, systemic inflammation, and blood lipid profiles: Wuhan-Zhuhai cohort study

Copper have been reported to be associated with metabolic diseases. However, results on copper exposure with blood lipid profiles are inconsistent, and the underlying mechanisms of this association remain unclear. This study focused on investigating associations between urinary copper and blood lipid profiles; and exploring the potential role of systemic inflammation in such relationships. Concentrations of urinary copper, plasma C-reactive protein (CRP), and four blood lipid parameters (e.g., Total cholesterol [TC], triglycerides [TG], low-density lipoprotein cholesterol [LDL-C], and high-density lipoprotein cholesterol [HDL-C]) were measured in the adult participants from Wuhan-Zhuhai cohort. The associations between copper, CRP, and four blood lipids were assessed by the multivariable linear regression models, and the 3D mesh graphs was used to examine the joint effects of copper exposure and CRP on four blood lipid parameters. In addition, we used mediation analysis to investigate the mediated effects of CRP in the relationships between copper exposure and blood lipid profiles. Each 1% increase in urinary copper was statistically significantly associated with a 5.32% (95% CI: 2.48%, 8.24%) increase in TG after adjusting for the confounders (P < 0.05). No significant associations were observed between urinary copper and the other three blood lipid parameters (all P > 0.05). In addition, urinary copper increased monotonically with plasma CRP elevation, which in turn, was positively associated with TC, TG, and LDL-C and negatively related to HDL-C (all P < 0.05). Results from 3D mesh graphs demonstrated that increased levels of plasma CRP with higher urinary copper corresponded to higher TC, TG, LDL-C, and lower HDL-C concentrations. Mediation analysis observed that CRP mediated 6.27% in the relationships of urinary copper and TG. These findings suggest that systemic inflammation partly mediated the association between copper exposure and abnormal blood lipid, and may contribute to the development of dyslipidemias.

Cardiovascular Outcome of Pediatric Patients With Bi-Allelic (Homozygous) Familial Hypercholesterolemia Before and After Initiation of Multimodal Lipid Lowering Therapy Including Lipoprotein Apheresis

Twenty-four patients with bi-allelic familial hypercholesterolemia commencing chronic lipoprotein apheresis (LA) at a mean age of 8.5 ± 3.1 years were analysed retrospectively and in part prospectively with a mean follow-up of 17.2 ± 5.6 years. Mean age at diagnosis was 6.3 ± 3.4 years. Untreated mean LDL-C concentrations were 752 mg/dl ± 193 mg/dl (19.5 mmol/l ± 5.0 mmol/l). Multimodal lipid lowering therapy including LA resulted in a mean LDL-C concentration of 184 mg/dl (4.8 mmol/l), which represents a 75.5% mean reduction. Proprotein convertase subtilisin/kexin type 9-antibodies contributed in 3 patients to LDL-C lowering with 5 patients remaining to be tested. After commencing chronic LA, 16 patients (67%) remained clinically stable with only subclinical findings of atherosclerotic cardiovascular disease (ASCVD), and neither cardiovascular events, nor need for vascular interventions or surgery. In 19 patients (79%), pathologic findings were detected at the aortic valve (AV), which in the majority were mild. AV replacement was required in 2 patients. Mean Lipoprotein(a) concentration was 42.4 mg/dl, 38% had >50 mg/dl. There was no overt correlation of AV pathologies with other ASCVD complications, or Lipoprotein(a) concentration. Physicochemical elimination of LDL particles by LA appears indispensable for patients with bi-allelic familial hypercholesterolemia and severe hypercholesterolemia to maximize the reduction of LDL-C. In conclusion, in this rare patient group regular assessment of both the AV, as well as all arteries accessible by ultrasound should be performed to adjust the intensity of multimodal lipid lowering therapy with the goal to prevent ASCVD events and aortic surgery.

Determinants and Prevalence of Metabolic Syndrome in Subjects Attending the General Outpatient Department of the Federal Medical Centre Katsina State, North West Nigeria

Metabolic Syndrome (MS) is a term that describe the presence of conditions that increase an individual risk for heart disease and other disorders such as diabetes and stroke, and its occurrence is in the rise in residents of North-Western Nigeria, The aim of this study was to investigate the prevalence and determinants of metabolic syndrome in respondents from Katsina senatorial zone attending the Out-patient Department of the Federal Medical Center Katsina, Katsina State, Nigeria. A total of 211 (male 109; female 102) respondents aged 10 to 80 years were recruited for the study. Anthropometric parameters and blood pressure of respondents were determined using standard methods; serum lipid profile was determined using enzymatic methods. From the results, 11.8% of the male respondents were under weight, 51.6% were within the normal range, 25.4% of the study male population was found to be overweight and 12.8% were obese. 13.5% of the female respondents were under weight, 51.9% were within the normal range, 22.8% of the study female population was found to be overweight and 13.1% were obese. All serum lipids measurements with the exception of serum LDL-C concentration correlated positively with age. There were no statistically significant differences between the frequencies of total cholesterol, HDL, LDL and TRIG between the male and female respondents. The most common form of Dyslipidemia in the male and female respondents is low HDL-C. BMI, SBP, LDL-C, HDLC and TRIG were associated metabolic syndrome with the association being significant for SBP and HDL-C (0.05; 0.03) in the male respondent, in the female respondents BMI, SBP, DBP, LDL-C and TRIG were associated metabolic syndrome with the association being significant for SBP, DBP, and TRIG (0.04; 0.04; 0.04) respectively. The prevalence of metabolic syndrome was highest in male (31.75%) than in the female respondents (28.33).The prevalence of metabolic syndrome is common in the population under study with the male respondents having the highest prevalence. A robust and well design intervention program by concerned authorities is desirable to address complications of the risk factors for metabolic syndrome in the population.

Management of familial hypercholesterolaemia in childhood.

All guidelines for the management of heterozygous familial hypercholesterolaemia in children and young people recommend statins to lower LDL-cholesterol (LDL-C) concentrations, to reduce the individual's adult risk of developing cardiovascular disease (CVD). Here, we review recent findings regarding the efficacy and safety of the use of stains in childhood. As expected from their safety profile in adults, there is no evidence from short-term trials or long-term follow-up that statin use in children is associated with any adverse effects on growth, pubertal development or muscle or liver toxicity. Long-term follow-up indicates benefits with respect to lower CVD rates. Factors that influence adherence are discussed, as is the role of the underlying genetic causes for hypercholesterolaemia and of variation at other genes in determining the LDL-C-lowering effect. Based on the good safety profile, and the expert opinion guidelines, clinicians should consider prescribing statins for children with hypercholesterolaemia from the age of at least 10 years (and earlier if CVD risk is particularly high in the family). Uptitrating statin dosage and the use of additional lipid-lowering therapies should be considered so that LDL-C concentrations are lowered to recommended targets.

Kangtaizhi Granule Alleviated Nonalcoholic Fatty Liver Disease in High-Fat Diet-Fed Rats and HepG2 Cells via AMPK/mTOR Signaling Pathway.

Kangtaizhi granule (KTZG) is a Chinese medicine compound prescription and has been proven to be effective in nonalcoholic fatty liver disease (NAFLD) treatment clinically. However, the underlying mechanisms under this efficacy are rather elusive. In the present study, network pharmacology and HPLC analysis were performed to identify the chemicals of KTZG and related target pathways for NAFLD treatment. Network pharmacology screened 42 compounds and 79 related targets related to NAFLD; HPLC analysis also confirmed six compounds in KTZG. Further experiments were also performed. In an in vivo study, SD rats were randomly divided into five groups: control (rats fed with normal diet), NAFLD (rats fed with high-fat diet), and KTZG 0.75, 1.5, and 3 groups (NAFLD rats treated with KTZG 0.75, 1.5, and 3 g/kg, respectively). Serum lipids were biochemically determined; hepatic steatosis and lipid accumulation were evaluated with HE and oil red O staining. In an in vitro study, HepG2 cells were incubated with 1 mM FFA to induce lipid accumulation with or without KTZG treatment. MTT assay, intracellular TG level, oil red O staining, and glucose uptake in cells were detected. Western blotting and immunohistochemical and immunofluorescence staining were also performed to determine the expression of lipid-related genes PPAR-γ, SREBP-1, p-AKT, FAS, and SIRT1 and genes in the AMPK/mTOR signaling pathway. In high-fat diet-fed rats, KTZG treatment significantly improved liver organ index and serum lipid contents of TG, TC, LDL-C, HDL-C, ALT, and AST significantly; HE and oil red O staining also showed that KTZG alleviated hepatic steatosis and liver lipid accumulation. In FFA-treated HepG2 cells, KTZG treatment decreased the intracellular TG levels, lipid accumulation, and attenuated glucose uptake significantly. More importantly, lipid-related genes PPAR-γ, SREBP-1, p-AKT, FAS, and SIRT1 expressions were ameliorated with KTZG treatment in high-fat diet-fed rats and FFA-induced HepG2 cells. The p-AMPK and p-mTOR expressions in the AMPK/mTOR signaling pathway were also modified with KTZG treatment in high-fat diet-fed rats and HepG2 cells. These results indicated that KTZG effectively ameliorated lipid accumulation and hepatic steatosis to prevent NAFLD in high-fat diet-fed rats and FFA-induced HepG2 cells, and this effect was associated with the AMPK/mTOR signaling pathway. Our results suggested that KTZG might be a potential therapeutic agent for the prevention of NAFLD.

The Association Between Serum Levels of Leptin and Lipid Profiles in Cardiovascular Patients With Valve Calcification

Adipose tissue-derived hormones known as adipokines, like leptin, have multiple bioactions. Notwithstanding the key roles of leptin in regulating energy homeostasis and metabolism, its cardiovascular functions are complex and not fully understood. This study aimed to investigate the association between serum concentrations of leptin and lipid profiles in patients with valve calcification. Seventy-two patients with valve calcification and 72 healthy individuals participated in this case-control study. The serum levels of biochemical markers and leptin were measured by the standard enzymatic methods and enzyme-linked immunosorbent assay (ELISA) technique, respectively. Significantly increased serum concentrations of FBS (P=0.001), urea (P&lt;0.0001), creatinine (P=0.018), P (P&lt;0.0001), LDL-C (P=0.011) and lower Ca (P=0.006), and HDL-C (P&lt;0.0001) levels were observed in patients compared to controls. There was no significant difference in the serum level of TG and TC of patients than controls. Systolic and diastolic blood pressures were significantly increased in patients relative to controls (P&lt;0.0001). However, a significantly diminished serum level of leptin was observed in patients than controls (P&lt;0.0001). The correlation analysis demonstrated that the serum leptin concentration is negatively correlated with creatinine, but it is positively correlated with systolic blood pressure (P=0.0302, P=0.0362, respectively). There was no statistically significant association between serum levels of leptin and lipid profiles. Our findings indicated dyslipidemia and reduced serum leptin concentrations in patients with valve calcification, suggesting the role of lipid abnormalities and reduced leptin levels in the development and pathogenesis of valve calcification diseases.

Author response: Low-density lipoprotein cholesterol and risk of intracerebral hemorrhage: A prospective study.

We thank Dr. Guo for the comment on our article.1 We did not collect specific information on statin use in the current study. We, thus, cannot examine whether statin use was associated with altered risk of intracerebral hemorrhage (ICH). Published studies regarding the relationship between statin use and ICH generated inconsistent results. For example, although Ribe et al.2 reported an association between statin use and reduced ICH risk, McKinney et al.3 reported a trend between low LDL-C concentrations due to statin therapy and higher ICH risk (OR, 1.08; 95% CI, 0.88–1.32; p = 0.47). Thus, more studies are warranted to understand a relationship between lipid-lowering medication use and risk of ICH.

Hypolipemic effects of histamine is due to inhibition of VLDL secretion from the liver: involvement of both H1 and H2-receptors

The research was performed to study the mechanism whereby histamine affects the profile of plasma lipids. Six groups of ten male rats were received two injections with histamine or its H1- and H2-agonists and antagonists. Histamine caused a significant decrease in the concentrations of triglyceride, total cholesterol, and LDLc, while HDLc had no significant change. The rate of VLDL secretion was 263.6 ± 25.8 mg/h dL in control rats and was inhibited by about 68% in histamine injected rats. These changes have been mimicked by either histamine H1- or H2-agonists. The effects of H1- and H2-agonists were abolished in the presence of cetirizine and famotidine respectively. Histamine causes a significant decrease in serum triglyceride, total, and LDL-cholesterol by both H1 and H2-receptors. The decrease in serum lipids is due to the inhibitory effect of histamine or its agonists on VLDL secretion from the liver.

Lipid Profile Results after Cardiovascular Prevention Programme: Euroaction Model in Spain.

Cardiovascular prevention and rehabilitation programmes (CVPRP) are an established model of care designed to improve risk factor management. They have been successfully implemented in a variety of settings, in patients with coronary heart disease (CHD). To assess the long term impact of a nurse-coordinated, multidisciplinary, CVPRP in patients with CHD in the reduction of lipid profile and medication prescription in clinical practice. The study used an analytical, experimental, population based, prospective and longitudinal design. In Spain, the study was conducted in the Valencian Community, including two randomized hospitals. Coronary patients were prospectively and consecutively identified in both hospitals. The intervention hospital carried out an 8-week CVPRP. The proportion of patients achieving improved standards of preventive care increased in the intervention hospital compared with the usual care hospital, mainly regarding LDL-C concentrations. Furthermore, an increased prescription of statins was found in the intervention group. However, there were no statistically significant differences in triglycerides and glucose levels. The EUROACTION nurse-led CVPRP enabled coronary patients to control lipid profile to the European targets. A large proportion of patients were prescribed statin therapy as cardioprotective medication with favorable changes in medication for coronary patients. To improve the potential for cardiovascular prevention, we need local preventive cardiology programmes adapted to the health policy of individual countries.

Comparison common equations for LDL-C calculation with direct assay and developing a novel formula in Iranian children and adolescents: the CASPIAN V study

BackgroundHypercholesterolemia is a common dyslipidemia that leads to atherosclerosis. It is proved that early stages of atherosclerosis begins in early stages of life. In several studies, widespread prevalence of dyslipidemia in children is reported. So, assessment of lipid profile in children and adolescence is necessary for early diagnosis of dyslipidemia. Laboratory methods for measuring LDL are not available and economical. So, in some laboratories Friedwald method is used to determine LDL level. But, the preciseness of this method is not acceptable. Further, the preciseness of this method was not assayed in children and adolescence. So, it seems that assaying the preciseness of different methods is necessary.MethodsThe methodology of this work is on the basis of findings of the Caspian V study. This study was conducted in 30 provinces of Iran during 2015. The population of this work was rural and urban students aged 7–18 years old. The level of total cholesterol (TC), HDL, LDL, and TG were measured using laboratory methods. The average and variances values were determined for each group of data using SPSS. Further, LDL values were calculated with a new formula introduced in this work. A comparison was made between the new formula and the other methods.ResultsIn the present study, we found that compare to four common formulas, Friedwald was the best equation to estimate LDL-C concentrations in Iranian children and adolescents and the new formula was the next accurate equation. The strongest correlation between Friedwald and the new equation was found for those with 15–18 years old.ConclusionConsidering the cut-off points of TG (100 mg/dL), we observed the strongest correlation between Friedwald equation and direct assay and the weakest one was for Ahmadi formula in subjects with either greater or lower TG concentrations. Furthermore, we found that Anandraja equation had the most sensitivity (89.5%), while the most specificity was dedicated to the new formula (98.9%).

Comparison between direct assay and popular equations for Low Density Lipoprotein-cholesterol estimation in Nepalese Population

Background: The aim of this study was to compare LDL-C estimations using various equations with directly measured LDL-C and to find the most accurate and reliable equation for measuring serum LDL-C at different triglycerides level.&#x0D; Materials and Methods: In this study, we performed a retrospective analysis on the database of our Laboratory Information System to retrieve results of lipid profile in patients visiting Dhulikhel Hospital during the period of 6 months. A total of 1420 participants were classified into three groups according to triglyceride (TG) concentrations as follows: &lt;150, 150–199 and &gt;199 mg/dL. LDL-C was calculated using the Friedewald, Chen, Vujovic, Hattori, Anandaraja and modified Friedewald equations and compared with directly measured LDL-C concentration (enzymatic method on Biosystems, BA-400).&#x0D; Results: In most of the instances, calculated LDL-C value was higher than the directly measured LDL-C values with negative mean difference with the exception of Hattori equation. The intraclass correlation coefficient (ICC) between the estimated and directly-measured LDL-C was higher with the Friedewald equation (ICC=0.917; 95% CI: 0.904-0.927) for all serum TG ranges compared with other equations. The reliability of all the equations was good with ICC being above 0.75 while that of the Friedewald equation was excellent in all the TG groups with ICC being above 0.9. Hattori equation was better in estimating LDL-C at normal TG range (ICC=0.927; 95% CI: 0.917-0.937) and borderline high TG (ICC= 0.933; 95% CI: 0.908-0.951).&#x0D; Conclusion: Calculated LDL-C using appropriate equations can be an alternative cost-effective tool to measure LDL-C when the direct measurement cannot be afforded.

SUN-560 Simvastatin Inhibits the Pro-Inflammatory and Pro-Atherogenic Effects of Cream in Obese Subjects

Our previous work has shown that the ingestion of cream induces an increase in oxidative stress and other cellular and molecular indices of inflammation and atherosclerosis and that treatment with Vytorin for 6 weeks reduced and reversed majority of the effects of cream. However, it is not clear which component of Vytorin, simvastatin or ezetimibe, is responsible for these intriguing and potent effects. Therefore, we further investigated the effects of simvastatin treatment on indices of inflammation and atherosclerosis at baseline and following intake of dairy cream. Ten obese patients with LDL >100mg/dl were given simvastatin 40mg/day for 6 weeks. Subjects were asked to ingest 33ml of cream (about 300 Calories) containing about 85% saturated fat. Fasting and post-cream intake blood samples were obtained at baseline and at 6 weeks. Total cholesterol and LDLc concentrations were lowered significantly at 6 weeks following simvastatin (p<0.05). Cream intake at 0 week induced significant increases in MNC expression of IL-1β (by 58±16%), TNF-α (by 79±19%), CD16 (by 103±32%), MMP-9 (by 68±17%), TLR-4 (by 68±12%) and TLR-2 (by 53±9%) over the baselines (p<0.05 for all). Cream intake at 0 week also induced a significant increase in IL-1β plasma concentrations by 94±18% over the baseline. Simvastatin treatment suppressed fasting levels of CD68 expression in MNC (by 38±9, p<0.05) and fasting plasma levels of IL-18 and MMP-9 (by 24±11% and 28±12%, respectively, p>0.05) compared to fasting levels at 0 week. The increase in IL-1β, TNFα, CD16 and MMP-9 expression in MNC following cream intake at end of simvastatin treatment was significantly suppressed (by 41±15%, 48±17%, 87±16% and 34±8%, respectively, p<0.05) compared to that before simvastatin treatment. In addition, there was a paradoxical suppression of the expression of TLR-2 and TLR-4 (by 30±11% and 24±9%, respectively) below baseline levels following cream at 6 weeks. Simvastatin treatment also suppressed cream induced increases in plasma IL-1β concentrations by 37±11% (p<0.05, compared to increases at 0 week). We conclude that simvastatin exerts a powerful anti-inflammatory effect and reduces expression of pro-inflammatory mediators induced by cream intake. This effect is similar in nature to that observed previously with Vytorin with some differences in the magnitude of the changes.

2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: The Task Force for diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD)

It has been demonstrated that diabetic dyslipidaemia is the chief bridge between diabetes and incremental risk of cardiovascular disease in patients with diabetes. However, the characteristics of lipoprotein subfractions distribution in patients with type 2 diabetes (T2D) have not been fully investigated. The aim of present study was to evaluate the distributions of lipoprotein subfractions in T2D patients.A total of 920 patients, who have not received lipid-lowering drug treatment previously, were consecutively enrolled in this study. Based on the evidence of diabetes, patients were divided into T2D group (n=204) and non-T2D group (n=716). Both low- and high-density lipoprotein cholesterol (LDL- and HDL-C) subfractions were analysed using the Quantimetrix Lipoprint System. The distributions of lipoprotein subfractions were evaluated in patients with and without T2D.Compared with non-T2D individuals, the T2D group manifested significantly lower large HDL-C concentration/HDL subfraction percentage, smaller mean LDL particle size but higher small HDL-C and LDL-C concentrations as well as small HDL and LDL subfraction percentages. Moreover, the data indicated that the small HDL-C/ LDL-C concentrations, the small and large HDL subfraction percentages along with the mean LDL particle size were independently related to the existence of T2D (95% CI=1.009–1.067, p=0.009; 95% CI=0.938-0.983, p=0.001; 95% CI=1.023–1.135, p=0.005; 95% CI= 1.005–1.048, p=0.014; 95% CI=0.940-0.999, p=0.040; respectively) assessed by logistic regression analysis.The present study indicated that the changes of lipid profile in patients with T2D are characterised by abnormal distributions of lipoprotein subfractions apart from clinically atherogenic dyslipidaemia.

A Study to Explore the LDLR Gene Polymorphisms Contribute to Atorvastatin Response in a Sample of Iraqi Population with Atherosclerotic Coronary Artery Disease

Genetic factors will determine the higher variability, which found in response to lipid reduction treatment (statins). However, due to ethnicity the frequency and effect of single nucleotide polymorphisms (SNPs) may differ. The main aim of lipid lowering medical treatment is to eventually prevent the endogenous production of cholesterol through inhibition of HMG-CoA reductase, The resulting decrease in hepatocyte cholesterol concentration triggers up-regulation of low-density lipoprotein (LDL)-receptor expression by inducing sterol regulatory element-binding protein (SREBP) 2 cleavage, as SREBP-2 activates LDL receptor transcription. The aim of this study was to evaluate the effects of low density lipoprotein receptor (LDL-R) gene variants (rs200727689; rs72658860) in response to atorvastatin treatment in atherosclerotic coronary artery disease (ACAD) in a sample of Iraqi patients. The genetic polymorphisms of rs200727689 and rs72658860 were studied in patients undergoing coronary angiography (CAG). One hundred Iraqi patients include 52 patients treated with 20mg/day and 48 patients treated with 40mg/day, In addition, 100 apparently healthy subjects were genotype for these SNP by the thermal profile of allelic discrimination methods used Real Time PCR (RT-PCR) assay. A significant increase in A allele frequency (rs200727689) compared with controls for total ACAD patients (43% vs 23.5%; OR= 2.46; 95% C.I: 1.60-3.77; p=0.000). For (rs72658860) SNP, among total patients the A allele also increased the frequency substantially compared with the controls (40.5% vs 23.5%; P=0.0003; OR= 2.22; 95% C.I: 1.44 -3.41). In the patients who were treated with atorvastatin, SNP rs72658860 AA genotype significantly affected the response of atorvastatin in dose 20mg compared with 40mg. The result showed in AA genotype of (rs200727689) SNP a reduction in TC concentrations (277.55±108.38 vs 326.99±63.56) and LDL-C concentrations (198.33±100.0 vs 250.01±62.52) in sera compared with GG genotype in patients treated with 20 mg atorvastatin, although, none in all parameters statistically significant differences.

Inhibition of JAK2/STAT3/SOCS3 signaling attenuates atherosclerosis in rabbit

BackgroundPrevious studies have indicated that the JAK/STAT signaling pathway is involved in modulating arterial adventitia inflammation response. In this study, we designed experiments to further investigate the effect of JAK2/STAT3/SOCS3 signaling in rabbit atherosclerosis process.MethodsAtherosclerosis was induced in the abdominal arteries of rabbits by balloon injury of the aorta supplemented by the atherogenic diet. Simultaneously, in the process of atherosclerosis, animals underwent either ruxolitinib treatment or not for 12 weeks. At the end of the experimental period, all rabbits were sacrificed. The plaque areas in abdominal artery, the lipid burden of plaque and the calcium burden of plaque were detected by H&E staining, Oil Red O staining and Alizarin Red staining, respectively. In addition, rabbit plasma lipids and inflammatory cytokines were measured by biochemical test kits or ELISA kits. Finally, the expression and phosphorylation levels of JAK2/STAT3/SOCS3 pathway-related proteins were detected by RT-qPCR, western blot and immunohistochemistry assays.ResultsH&E staining and CT scan analysis showed that rabbit atherosclerosis model was constructed successfully. Ruxolitinib, an inhibitor of the Janus kinase 2 (JAK2), substantially reduced the area of atherosclerotic plaques in rabbits treated with high fat diet and balloon injury of the aorta. Moreover, ruxolitinib significantly decreased IL-6, IL-1β, IFN-γ and TNF-α, but increased IL-10 and IL-17 levels in plasma of atherosclerotic rabbits. Additionally, ruxolitinib reduced plasma TC, TG and LDL-C contents and AIP value, while enhanced HDL-C level in atherosclerotic rabbits. Furthermore, we found that JAK2 and STAT3 phosphorylation were up-regulated in rabbits with atherosclerosis when compared with those of the control group, followed by the expression of SOCS3 was also increased due to the activation of JAK2 and STAT3. Interestingly, ruxolitinib could inactivate JAK2 and STAT3 pathway and decrease SOCS3 expression.ConclusionTaken together, the inhibition of JAK2/STAT3/SOCS3 signaling pathway may be a novel method for the clinical treatment of artery atherosclerosis.

Dietary cholesterol level affects growth, molting performance and ecdysteroid signal transduction in Procambarus clarkii

The effects of dietary cholesterol supplementation on growth, molting performance and ecdysteroid signal transduction of juvenile crayfish Procambarus clarkii (initial weight = 3.55 ± 0.03 g) were evaluated over a 6-week feeding trial. The crude protein and lipid level of basal diet was targeted at 27% and 6%, respectively. Five levels of supplemented cholesterol (0, 0.25, 0.50, 0.75, and 1.00%) resulted in diets analyzed to contain 0.06, 0.29, 0.54, 0.81, and 1.05% cholesterol. Final weight, weight gain, feed intake, molting times, molting rate, chitinase mRNA expression and hemolymphatic LDL-C content significantly increased (P < .01) as the cholesterol supplementation level increased from 0.00 to 0.50%, and then significantly decreased (P < .05) as the cholesterol supplementation level increased from 0.50 to 1.00%. P. clarkii fed with 0.25% cholesterol supplementation and without cholesterol supplementation had significantly higher MIH expression level compared to P. clarkii fed with 0.50 and 0.75% cholesterol supplementation. Total cholesterol content in the hemolymph, hepatopancreas, and intestine, as well as hemolymphatic HDL-C content of P. increased significantly as the cholesterol supplementation increased from 0.00 to 1.00%. Taken together, the results presented here indicated that P. clarkii juvenile would grow better when fed with a 27% protein and 6% lipid diet supplemented with 0.50% cholesterol. The reason might be that more cholesterol transported from hepatopancreas resulted in the variation of ecdysteroid signal transduction, ultimately leading to increasing molting times in P. clarkii fed diets with 0.50% cholesterol supplementation.

Abstract 52: Plasma Metabolomic Signatures of the American Heart Association Diet Score: Findings From the Boston Puerto Rican Health Study

Introduction: Puerto Rican adults living on the US mainland tend to have poor quality diets and adverse cardiometabolic risk. Plasma metabolomic signatures reflect dietary intakes and variability in metabolic response to diet. Hypothesis: A plasma metabolomic signature reflecting adherence to the American Heart Association (AHA) dietary guidelines will be associated with cardiometabolic risk. Methods: We used LC/MS to measure plasma metabolites (&gt;700) among Boston Puerto Rican Health Study participants, aged 45-75 years, without (n=252) and with (n=254) type 2 diabetes (T2D). We calculated a modified version of a previously validated AHA diet score (AHA-DS), which included variety and amounts of fruits/vegetables, whole grains, fish, saturated fat, trans fat, sodium, and added sugars. We used elastic net regression to identify a metabolomic signature that associated with higher adherence to the AHA-DS among those without T2D (training set) and replicated the associations among those with T2D (testing set). A metabolomic score was calculated as the weighted sum of the diet associated metabolites. We used general linear models to determine the cross-sectional associations between the AHA-DS, metabolomic score, and cardiometabolic risk factors. Results: A diet-associated metabolomic signature with 58 metabolites, primarily lipids and amino acids, was identified. This metabolomic score correlated moderately with the AHA-DS among those with and without T2D (r=0.42-0.46, P &lt;5.7x10 -12 ). In all participants (n=506), the metabolomic score, but not the AHA-DS, was significantly associated with higher HDL-C and LDL-C concentrations, and lower waist circumference ( P &lt;0.004; Table 1). No associations were observed for triglyceride concentrations, glycemia measures, or blood pressure. Conclusions: In individuals of Puerto Rican descent, we identified a metabolomic signature that reflected adherence and metabolic response to the AHA dietary guidelines and that associated with cardiometabolic risk factors.

2019 ESC/EAS Guidelines for Dyslipidaemia – What’s New?

Abstract The European Society of Cardiology and the European Atherosclerotic Society are recommending in the 2019 guideline for dyslipidemia the best management strategies for an individual patient with a given condition. The guideline recommends the use of new tests to help identify high-risk patients. These include both coronary artery calcium imaging and biomarker tests. Modifications have also been made to the risk stratification categories, so that patients with atherosclerotic artery disease, diabetes mellitus with target organ damage, familial hypercholesterolaemia and severe chronic kidney disease are all included in very-high risk patients. The new ESC/EAS guideline for dyslipidemia management compared with the 2016 version include more intensive reduction of LDL-c across CV risk categories. If the goals are not achieved with the maximum tolerated dose of statin, combination with ezetimibe is recommended. An important message of the new guideline is that until this moment there are no known adverse effects of very low LDL-c concentrations.