Control Low Density Lipoprotein Research Articles

Non-invasive lipid panel of MASLD fibrosis transition underscores the role of lipoprotein sulfatides in hepatic immunomodulation.

There exists a pressing need for a non-invasive panel that differentiates mild fibrosis from non-fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD). In this work, we applied quantitative lipidomics and sterolomics on sera from the PERSONS cohort with biopsy-based histological assessment of liver pathology. We trained a lasso regression model using quantitative omics data and clinical variables, deriving a combinatorial panel of lipids and clinical indices that differentiates mild fibrosis (>F1, n= 324) from non-fibrosis (F0, n= 195), with an area under receiver operating characteristic curve (AUROC) at 0.775 (95% confidence interval [CI]: 0.735-0.816). Circulating sulfatides (SLs) emerged as central lipids distinctly associated with fibrosis pathogenesis in MASLD. Lipidomics analysis of lipoprotein fractions revealed a redistribution of circulating SLs from high-density lipoproteins (HDLs) onto low-density lipoproteins (LDLs) in MASLD fibrosis. We further verified that patient LDLs with reduced SL content triggered a smaller activation of type II natural killer T lymphocytes, compared with control LDLs. Our results suggest that hepatic crosstalk with systemic immunity mediated by lipoprotein metabolism underlies fibrosis progression at early-stage MASLD.

Pengaruh Konsumsi Timun dan Bawang Merah terhadap Penurunan Kadar Kolesterol Pasien di Wilayah Kerja Puskesmas Babakan

Hypercholesterolemia is caused by the liver not being able to control LDL in the blood vessels, this condition will cause atherosclerosis and cardiovascular disease. Sterols and flavonoids are content that found in cucumbers which can lower cholesterol by replacing sterols with LDL which will be absorbed in the digestive system. The LDL will be excreted in the form of feces with the help of flavonoids And quercetin is a content found in red onions that can reduce cholesterol levels in the blood by inhibiting the HMG Co-A reductase enzyme. Yankestrad is a program at the Babakan Public Health Center include the use of medicinal plants (TOGA) such as cucumbers and red onions. The purpose of this study is to know the effect of cucumber and red onions consumption on reducing cholesterol levels in patients in the Babakan Health Center work area through the Yankestrad program. Research methods are analytical observational with case control research design and purposive sampling methods. The results of this there is an effect of consuming cucumber and red onions on reducing cholesterol levels.

Abstract 16934: Eicosapentaenoic Acid Inhibits Lipoprotein(a) With Higher Rates of Oxidation Compared to Non-Modified Low-Density Lipoprotein in vitro

Background: Lp(a) synthesis is the result of covalent binding of apolipoprotein a to apolipoprotein B on LDL particles. Elevated Lp(a) levels are an independent and causal risk factor for cardiovascular (CV) disease. Atherogenic mechanisms for Lp(a) include increased inflammation due to its associated oxidized lipids. The omega-3 fatty acid (n3-FA) EPA administered as icosapent ethyl reduced CV events in REDUCE-IT. As a potential mechanism, EPA inhibits oxidation of different sized ApoB-containing lipoproteins compared to other n3-FAs. We tested EPA effects on oxidation of lipoprotein samples enriched with Lp(a) compared to control LDL samples. Methods: Lp(a) was enriched to 40% of total ApoB-containing particles from patients with elevated levels by isopycnic centrifugation. Samples of Lp(a) (100 μg/mL) and non-modified LDL were incubated at 37°C for 30 min with EPA (50 μM). Samples were then subjected to copper sulfate-induced oxidation (20 μM) monitored by formation of malondialdehyde (MDA). Results: Lp(a) enriched ApoB particles underwent increased oxidation by 18% after 2 h which was significantly higher than non-modified LDL (13.24 ± 0.47 vs 11.23 ± 0.44 μM, p<0.001). EPA significantly inhibited Lp(a) and non-modified LDL oxidation; after 2 h, EPA inhibited MDA levels by 56% and 76%, respectively (p<0.001). The inhibition of oxidation in both particles with EPA was time dependent. Conclusions: Lp(a) enriched plasma underwent oxidation to a greater extent than non-modified LDL and this process was inhibited in a dose-dependent fashion by EPA. The antioxidant actions of EPA may contribute to reduced events in outcome trials, including in subjects with elevated Lp(a).

LDL binding to cell receptors and extracellular matrix is proatherogenic in obesity but improves after bariatric surgery

Obesity is a major global public health issue involving dyslipidemia, oxidative stress, inflammation, and increased risk of CVD. Weight loss reduces this risk, but the biochemical underpinnings are unclear. We explored how obesity and weight loss after bariatric surgery influence LDL interactions that trigger proatherogenic versus antiatherogenic processes. LDL was isolated from plasma of six patients with severe obesity before (basal) and 6–12 months after bariatric surgery (basal BMI = 42.7 kg/m2; 6-months and 12-months postoperative BMI = 34.1 and 30 kg/m2). Control LDL were from six healthy subjects (BMI = 22.6 kg/m2). LDL binding was quantified by ELISA; LDL size and charge were assessed by chromatography; LDL biochemical composition was determined. Compared to controls, basal LDL showed decreased nonatherogenic binding to LDL receptor, which improved postoperatively. Conversely, basal LDL showed increased binding to scavenger receptors LOX1 and CD36 and to glycosaminoglycans, fibronectin and collagen, which is proatherogenic. One year postoperatively, this binding decreased but remained elevated, consistent with elevated lipid peroxidation. Serum amyloid A and nonesterified fatty acids were elevated in basal and postoperative LDL, indicating obesity-associated inflammation. Aggregated and electronegative LDL remained elevated, suggesting proatherogenic processes. These results suggest that obesity-induced inflammation contributes to harmful LDL alterations that probably increase the risk of CVD. We conclude that in obesity, LDL interactions with cell receptors and extracellular matrix shift in a proatherogenic manner but are partially reversed upon postoperative weight loss. These results help explain why the risk of CVD increases in obesity but decreases upon weight loss.

1250-P: Clinical and Demographic Characteristics of Patients with Coexistent Type 2 Diabetes, Hypertension, and Dyslipidemia—Results from the Largest Retrospective EMR Study from India

Introduction: Common manifestations of end-organ damage due to diabetes, dyslipidemia and hypertension, predispose patients to develop cardiovascular diseases (CVD). The data on triple disease in India is scarce. In patients with triple disease, CVD risk is amplified, necessitating better understanding of their current clinical characteristics and care gaps. Aims and Methods: This was an EMR based, retrospective, multicenter, cross sectional, database study to evaluate the demographic and clinical profile of adult patients with age more than 18 years having coexistent type 2 DM, dyslipidemia, and hypertension in India. Data of patients with type 1 DM, FH and pregnancy were excluded. Results: Data of 6722173 patients with age ≥18 years registered in EMR from Jan ‘21 to Dec ‘21 was extracted from the EMR database. Out of these patients, 427835 (6.36%) were found to have coexistent hypertension, type 2 DM and dyslipidemia. Mean age was 59.92 years and 57% were males. The mean BMI was 28.07 kg/m2, and 73% had an above normal BMI (>24.99). The mean SBP and DBP in mmHg were noted to be 138.81 and 82.17, respectively. Only 10% and 28% of patients had a normal SBP and normal DBP, respectively. The mean HbA1c was 8.35% with only 27% having HbA1C <7%. The mean (% optimal control) LDL, total cholesterol, triglycerides in mg/dl (%) was 98.38 (44), 174.75 (28), and 181.42 (56), respectively. ARBs (25%) and combination of anti-hypertensive with diuretics (14%) were most used for hypertension treatment. Statin alone was used in 38% of patients while statin in combination with other drugs was used in 56%. Biguanides alone and its combination with sulphonylureas were used in 74.6% and 41% of patients with diabetes, respectively. Conclusion: The findings suggests that control of triple disease in India is inadequate despite therapy. There is need to optimize management of triple disease. Disclosure V.Natarajan: Employee; Dr. Reddy’s Laboratories Ltd. G.D.Dhanaki: None. R.T.Rathod: None. B.P.Kotak: Employee; Dr. Reddy’s Laboratories Ltd. R.Chawla: None. J.Dalal: None. P.Chandra: None. V.Kumar: None. V.Ayyar: None. R.S.Badani: None. M.Syed: None. K.Gaurav: None.

Identification and Functional Analysis of APOB Variants in a Cohort of Hypercholesterolemic Patients.

Mutations in APOB are the second most frequent cause of familial hypercholesterolemia (FH). APOB is highly polymorphic, and many variants are benign or of uncertain significance, so functional analysis is necessary to ascertain their pathogenicity. Our aim was to identify and characterize APOB variants in patients with hypercholesterolemia. Index patients (n = 825) with clinically suspected FH were analyzed using next-generation sequencing. In total, 40% of the patients presented a variant in LDLR, APOB, PCSK9 or LDLRAP1, with 12% of the variants in APOB. These variants showed frequencies in the general population lower than 0.5% and were classified as damaging and/or probably damaging by 3 or more predictors of pathogenicity. The variants c.10030A>G;p.(Lys3344Glu) and c.11401T>A;p.(Ser3801Thr) were characterized. The p.(Lys3344Glu) variant co-segregated with high low-density lipoprotein (LDL)-cholesterol in 2 families studied. LDL isolated from apoB p.(Lys3344Glu) heterozygous patients showed reduced ability to compete with fluorescently-labelled LDL for cellular binding and uptake compared with control LDL and was markedly deficient in supporting U937 cell proliferation. LDL that was carrying apoB p.(Ser3801Thr) was not defective in competing with control LDL for cellular binding and uptake. We conclude that the apoB p.(Lys3344Glu) variant is defective in the interaction with the LDL receptor and is causative of FH, whereas the apoB p.(Ser3801Thr) variant is benign.

Hypothyroidism, Hyperthyroidism and its Relationship with Lipid Profile in Thyroid Dysfunction Patients

Background: -
 Thyroid hormone synthesis is necessary for the growth, development, and healthy function of all body organs. Because thyroid malfunction causes a considerable shift in lipid levels, It is well known that thyroid hormones influence how lipid and lipoprotein metabolism is regulated. An essential regulator of intermediate metabolism are thyroid hormones. The purpose This study's objective was to look at the relationship between thyroid dysfunction patients' lipid profiles, hypothyroidism, and hyperthyroidism ..
 Materials and Methods:-
 In this study, the EIA method was used to evaluate the levels of T4, thyronine, and TSH in a sample of 50 patients and 50 healthy individuals. When assessing TG, LDL , TC ,and HDL , A fully automated biochemistry analyzer was employed.
 Results:-
 According to our research, HDL values are much lower in hypothyroidism cases compared to hyperthyroidism and control subjects, whereas TC, LDL, VLDL, and TG levels are significantly greater. When compared to control persons. Serum levels of, TG, TC, LDL, and VLDL are much lower in hyperthyroidism patients On the basis of a clinical examination of thyroid hormone., we found T4,T3 in serum sample wear higher than in control in hyperthyroid group while TSH wear low. In hypothyroid sample we found on the contrary .
 Conclusion:-
 In this research we found a significant correlation between thyroid dysfunction and lipid profile

Ethnicity based differences in statin use and hypercholesterolemia control among patients with premature coronary artery disease-results of I-PAD study

BackgroundStatins use is the most important treatment for high LDL cholesterol in patients with premature coronary artery disease (CAD). Previous reports have shown racial and gender differences in statin use in the general population, but this wasn't studied in premature CAD based on different ethnicities. Methods and resultsOur study includes 1917 men and women with confirmed diagnosis of premature CAD. Logistic regression model was used to evaluate the high LDL cholesterol control in the groups and the OR with 95% confidence interval (CI) was reported as the effect size. After adjustment for confounders, the odds of controlling LDL in women taking Lovastatin, Rosuvastatin, and Simvastatin were 0.27 (0.03, 0.45) lower in comparison with men. Also, in participant who took 3 types of statins, the odds of controlling LDL were significantly different between Lor and Arab compared with Fars ethnicity. After adjustment to all confounders (full model), the odds of controlling LDL were lower for Gilak in Lovastatin, Rosuvastatin, and Simvastatin by 0.64 (0.47, 0.75); 0.61 (0.43, 0.73); 0.63 (0.46, 0.74) respectively and higher for Arab in Lovastatin, Rosuvastatin, and Simvastatin by 4.63 (18.28, 0.73); 4.67 (17.47, 0.74); 4.55 (17.03, 0.71) respectively compared to Fars. ConclusionsMajor differences in different gender and ethnicities may have had led to disparities in statin use and LDL control. Awareness of the statins impact on high LDL cholesterol based on different ethnicities can help health decision-makers to close the observed gaps in statin use and control LDL to prevent CAD problems.

Evaluation of Thiol/Disulfide Homeostasis and Neurogenin 3 Levels as a Marker of Oxidative Stress in Children and Adolescents Newly Diagnosed with Type 1 Diabetes

The objective of the study was to determine the relationship between autoimmunity and dynamic thiol/disulfide, neurogenin 3 (ngn 3) status in the newly diagnosed with type 1 diabetes mellitus (T1DM), the level of treatment, and thiol/disulfide homeostasis and neurogenin 3, and to found the changes in neurogenin 3 level due to beta cell damage in children newly diagnosed with T1DM. Totally 60 children aged 1-18 years old, 30 of them newly diagnosed with type 1 diabetes (patients), and 30 of them healthy children in the same age group (control) were included in the study. Insulin and C-peptide levels of newly diagnosed T1DM patients were lower than the control group, however, HbA1c, glucose, creatinine, cholesterol, triglyceride, and LDL levels were found higher in patients. Total thiol level and Gad antibody positive rate were found higher in children newly diagnosed with T1DM. In addition, it was observed that the rate of anti-insulin antibody positivity increased in the 6th-month control of patients. However, HbA1c and glucose levels at diagnosis were higher in patients compared to the control group at the sixth month. Insulin and C-peptide levels were determined lower in patients admitted with diabetic ketoacidosis. A negative correlation was observed between native thiol and anti-insulin antibody parameters and a positive correlation between ngn 3 and total cholesterol and LDL. In conclusion, thiol/disulfide homeostasis and ngn 3 parameters can be used as oxidative stress markers in children and adolescents newly diagnosed with T1DM.

Ezetimibe and diabetes mellitus:a new strategy for lowering cholesterol

Diabetes mellitus is a well-recognized risk factor for cardiovascular diseases, so an “aggressive” therapeutic approach is necessary for some high-risk patients. Low-density lipoprotein (LDL) cholesterol is the leading modifiable risk factor for the development of atherosclerotic cardiovascular diseases (ACVD). It is known that statins are the gold standard to control LDL cholesterol and reduce the risks associated with ACVD; however, many patients do not achieve their LDL cholesterol target or are unable to use this class of drugs due to associated side effects. Recent studies of non-statin cholesterol-lowering drugs (ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors) have demonstrated benefits in the treatment of ACVD, and new drugs (bempedoic acid, inclisiran) have shown promising results in preclinical and clinical studies. New evidence suggests that prescription of ezetimibe as an addition to statins provides an additional cardioprotective effect. This review aims to discuss the role of ezetimibe in the treatment of patients with diabetes mellitus and dyslipoproteinemia and to consider its efficacy and safety. The combined use of low- or moderate-intensity therapy with statins and ezetimibe involves two complementary mechanisms: a decrease in the intracellular concentration of cholesterol with increased uptake of LDL cholesterol by hepatocytes and a decrease in cholesterol absorption in the intestines. These mechanisms act synergistically and can provide the same overall effect as when using high-intensity statin therapy. The safety of combined therapy is equivalent to that of monotherapy with HMG-CoA reductase inhibitors in similar doses. This combination is generally better tolerated than high doses of HMG-CoA reductase inhibitors and has advantages in patients at risk of myopathy and statin-induced type 2 diabetes. Thus, despite some caveats, ezetimibe remains the drug of choice in the arsenal of pharmacological agents.

Potential Effect of Syzygium aromaticum (Cloves) Extract on Serum Antioxidant Status and Lipid Profiles in Wistar Rats with Artesunate Toxicity

Artesunate toxicity has been linked to increased production of reactive oxygen species resulting in oxidative stress, which has been implicated in the pathogenesis of many chronic diseases. This study evaluated the effects of hydroethanolic extract of Syzygium aromaticum buds (HESAB) on serum antioxidant status and lipid profiles in Wistar rats with artesunate toxicity. Forty-eight male Wistar rats (150–200 g) randomized into six groups (n = 8) were treated as follows for 21 days: Group 1 (Control; DMSO); Group 2 (Artesunate, 15 mg/kg only); Group 3 (HESAB only, 400 mg/kg); Group 4 (HESAB only, 800 mg/kg); Group 5 (Artesunate, 15 mg/kg + HESAB, 400 mg/kg); Group 6 (Artesunate, 15 mg/kg + HESAB, 800 mg/kg). Antioxidant parameters—such as malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO), glutathione (GSH), glutathione peroxidase (GPx), and catalase (CAT)—were assayed in the serum using established methods. Serum lipid profiles—which include total cholesterol (TC), triglyceride (TAG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) assays—were performed using kits. The findings showed a significant increase in lipid profile of the artesunate-induced group compared to the control and treated groups. Administration of HESAB reversed the toxic effects of artesunate. The levels of TC (69.42 ± 8.03 mg/dL, TAG (34.43 ± 6.04 mg/dL), and LDL (45.1 ± 9.66 mg/dL) in the untreated group were significantly higher than the control group TC (41.42 ± 7.57 mg/dL), TAG (28.18 ± 1.58 mg/dL), and LDL (27.73 ± 5.00 mg/dL). The antioxidant profile however was significantly reduced in the diseased (artesunate) group compared to control and treated groups. MDA, NO, and GSH levels in the untreated group were 5.032 ± 1.25 µmol/L, 10.65 ± 3.84 µmol/L, and 0.20 ± 0.145 μM respectively and 2.237 ± 0.95 µmol/L, 6.20 ± 2.21 µmol/L, and 0.49 ± 0.068 μM in control group respectively. Treatment with HESAB raised the GSH level to 0.38 ± 0.19 μM. Furthermore, CAT, SOD, and GPX were 7.62 ± 2.15, 2.76 ± 1.52, and 3.54 ± 1.91 μmol/mL in untreated group respectively and 19.03 ± 4.25, 8.05 ± 2.91, and 10.62 ± 3.24 μmol/mL in control group respectively. Treatment with HESAB raised the CAT, SOD, and GPX to 18.866 ± 2.59, 5.020 ± 0.89, and 5.05 ± 2.01 μmol/mL respectively. In conclusion, artesunate toxicity caused a significant increase in lipid profiles and decrease in antioxidant level in the rats’ serum while administration of S. aromaticum bud extract lowered lipid levels and raised the antioxidant status.

Gender disparity in prevalence and risk factors of chronic Kidney disease among patients with type 2 diabetes in Northeastern Nigeria.

Introduction: Diabetes mellitus is a metabolic disorder that is responsible for up to 5% of premature deaths worldwide. Diabetic kidney disease is the leading cause of end-stage renal disease. This study aims to evaluate gender disparity in prevalence and risk factors of diabetic kidney disease in northeastern Nigeria. Methodology: The study population consisted of adult patients with type 2 diabetesrecruited consecutively at the diabetes clinic of the University of Maiduguri Teaching Hospital, Maiduguri. Socio-demographic and anthropometric variables including age, sex, weight, height, BMI, as well as laboratory parameters, were obtained from each patient. Glomerular filtration rate was derived from the CKD-EPI formula using serum creatinine. Results: Two hundred and sixty-one adult patients with type 2 diabetes were recruited consecutively from the Diabetes outpatient clinic of the University of Maiduguri Teaching Hospital, Maiduguri. There were 167(64%) females and 94(36%) males. The mean ages of males and females were 51.10±12.23 years and 48.76±11.00 years, respectively (p= 0.115). The mean duration of diabetes was similar between males and females (7.24±7.18 vs 6.87±6.02 years, p= 0.652). Females had a higher BMI compared with males (28.49±6.27Kg/M2 vs 26.41±4.86Kg/M2 p= 0.003). Fasting blood glucose, Low-density lipoprotein cholesterol and PCV were more deranged in females than among males (9.53±4.72 mmol/L vs 11.10±5.97mmol/L p= 0.020; 2.84±1.03mmol/L vs 3.19±1.03mmol/L p=0.009; 34.49±5.33% vs 33.11±4.54% p= 0.026). Out of the study population, 83(74.1%) females had renal dysfunction compared with 29(25.9%) males. The risk factors for progressive kidney disease among female patients were age >45 years (Exp (B) 1.799, 95% CI= 1.165-3.805)and systolic blood pressure >140mmHg (Exp (B)= 1.592, 95% CI= 0.772- 3.284). Conclusion: Diabetic kidney disease among our cohorts with type 2 diabetes was more prevalent among females compared with males and the risk factors associated with this disparity were older age, high BMI, poor glycaemic control, low PCV and elevated LDL cholesterol.

Gender disparity in prevalence and risk factors of chronic Kidney disease among patients with type 2 diabetes in Northeastern Nigeria.

ABSTRACT Introduction: Diabetes mellitus is a metabolic disorder that is responsible for up to 5% of premature deaths worldwide. Diabetic kidney disease is the leading cause of end-stage renal disease. This study aims to evaluate gender disparity in prevalence and risk factors of diabetic kidney disease in northeastern Nigeria. Methodology: The study population consisted of adult patients with type 2 diabetesrecruited consecutively at the diabetes clinic of the University of Maiduguri Teaching Hospital, Maiduguri. Socio-demographic and anthropometric variables including age, sex, weight, height, BMI, as well as laboratory parameters, were obtained from each patient. Glomerular filtration rate was derived from the CKD-EPI formula using serum creatinine. Results: Two hundred and sixty-one adult patients with type 2 diabetes were recruited consecutively from the Diabetes outpatient clinic of the University of Maiduguri Teaching Hospital, Maiduguri. There were 167(64%) females and 94(36%) males. The mean ages of males and females were 51.10±12.23 years and 48.76±11.00 years, respectively (p= 0.115). The mean duration of diabetes was similar between males and females (7.24±7.18 vs 6.87±6.02 years, p= 0.652). Females had a higher BMI compared with males (28.49±6.27Kg/M2 vs 26.41±4.86Kg/M2 p= 0.003). Fasting blood glucose, Low-density lipoprotein cholesterol and PCV were more deranged in females than among males (9.53±4.72 mmol/L vs 11.10±5.97mmol/L p= 0.020; 2.84±1.03mmol/L vs 3.19±1.03mmol/L p=0.009; 34.49±5.33% vs 33.11±4.54% p= 0.026). Out of the study population, 83(74.1%) females had renal dysfunction compared with 29(25.9%) males. The risk factors for progressive kidney disease among female patients were age >45 years (Exp (B) 1.799, 95% CI= 1.165-3.805)and systolic blood pressure >140mmHg (Exp (B)= 1.592, 95% CI= 0.772- 3.284). Conclusion: Diabetic kidney disease among our cohorts with type 2 diabetes was more prevalent among females compared with males and the risk factors associated with this disparity were older age, high BMI, poor glycaemic control, low PCV and elevated LDL cholesterol. Keywords: Diabetic kidney disease, Gender difference, Prevalence, Risk factors

Patient portal engagement and diabetes management among new portal users in the Veterans Health Administration.

The study sought to investigate whether consistent use of the Veterans Health Administration's My HealtheVet (MHV) online patient portal is associated with improvement in diabetes-related physiological measures among new portal users. We conducted a retrospective cohort study of new portal users with type 2 diabetes that registered for MHV between 2012 and 2016. We used random-effect linear regression models to examine associations between months of portal use in a year (consistency) and annual means of the physiological measures (hemoglobin A1c [HbA1c], low-density lipoproteins [LDLs], and blood pressure [BP]) in the first 3 years of portal use. For patients with uncontrolled HbA1c, LDL, or BP at baseline, more months of portal use in a year was associated with greater improvement. Compared with 1 month of use, using the portal 12 months in a year was associated with annual declines in HbA1c of -0.41% (95% confidence interval [CI], -0.46% to -0.36%) and in LDL of -6.25 (95% CI, -7.15 to -5.36) mg/dL. Twelve months of portal use was associated with minimal improvements in BP: systolic BP of -1.01 (95% CI, -1.33 to -0.68) mm Hg and diastolic BP of -0.67 (95% CI, -0.85 to -0.49) mm Hg. All associations were smaller or not present for patients in control of these measures at baseline. We found consistent use of the patient portal among new portal users to be associated with modest improvements in mean HbA1c and LDL for patients at increased risk at baseline. For patients with type 2 diabetes, self-management supported by online patient portals may help control HbA1c, LDL, and BP.

CD36 Promotes Platelet Phosphatidylserine Exposure through MAP Kinase ERK5

Dyslipidemic conditions can promote atherosclerotic plaque instability and rupture, leading to thrombosis that can cause life threatening complications. Thrombosis in this setting is augmented by circulating oxidized lipids on oxidized low density lipoprotein particles (oxLDL) that are recognized by key scavenger receptors. CD36 is a major platelet scavenger receptor that recognizes oxLDL and consequently promotes a prothrombotic platelet phenotype through multiple signaling pathways. We previously reported that recognition of oxLDL by CD36 generates specific reactive oxygen species through Src family kinases and NADPH oxidase. These species modulate redox sensitive signaling, such as the activation of the oxidant sensor MAP kinase ERK5, leading to platelet integrin activation, aggregation, and thrombus formation. Although ERK5 was a key effector for CD36 to promote thrombosis, the downstream signaling mechanisms are unclear. We hypothesize that CD36 promotes a procoagulant phenotype that requires ERK5. Platelets isolated and washed from healthy human donors were stimulated with buffer, native low-density lipoprotein (LDL), or oxLDL, and were stained with fluorophore-conjugated Annexin V or Lactadherin to detect exposure of procoagulant phosphatidylserine (PS). OxLDL-stimulated platelets showed dose-dependent 13.4 ± 2.8% and 18.5 ± 3.5% increases in Lactadherin binding at 50 and 100μg/mL oxLDL compared to control LDL (p=0.026; p<0.01), and a rapid binding within 5 min (11.0±0.35%, p<0.001). Furthermore, pre-treatment with oxLDL followed by addition of convulxin, a snake venom that activates platelets through the collagen signaling receptor GPVI, showed a 58.1 ± 4.62% increase in Lactadherin binding compared to oxLDL and convulxin alone (p<0.0001). Addition of ADP or thrombin, agonists that activates specific G-protein coupled receptors, following pre-treatment with oxLDL did not enhance Lactadherin binding. Platelets treated with FA6, a monoclonal CD36 antibody which prevents oxLDL binding, or BIX02188, an ERK5 inhibitor, showed an 80-90% decrease in Annexin V binding (p=0.039; p=0.02) after oxLDL exposure compared to a control non-immunizing IgG or DMSO. To link known pathways for PS exposure with oxLDL-induced PS exposure, platelets were stimulated with oxLDL followed by treatment with Z-VAD-FMK, a “pan” caspase inhibitor, or cyclosporin A, a cyclophilin D/mitochondrial permeability transition pore inhibitor. Z-VAD-FMK treated platelets showed 68% decrease in Lactadherin binding compared to control DMSO (p=0.0196), whereas cyclosporin A did not inhibit Lactadherin binding. Relevance of CD36/ERK5-mediated PS exposure was demonstrated using an in vivo arterial thrombosis model that relies on autologous transplantation of the epigastric artery, which has an adventitial surface that serves as a collagen-rich thrombogenic substrate for thrombosis, into the carotid artery. This model of thrombosis was chosen due to the potential impact of free radical generation in the standard ferric chloride or Rose Bengal-mediated arterial thrombosis models. Bone marrows from platelet ERK5-deficient mice (ERK5 flox/Pf4-cre+) or control mice (ERK5 flox/flox) were transplanted into irradiated atherogenic apoE null mice fed a high fat or control diet. Fibrin deposition, detected by a fluorophore-conjugated antibody to fibrin, was enhanced in hyperlipidemic conditions for mice with platelet ERK5. High fat diet-fed chimeric mice without ERK5 or animals on control diet do not show enhanced fibrin deposition. In conclusion, oxLDL promoted PS exposure through a CD36-Src family kinases-ERK5-caspase-dependent mechanism. PS exposure by this pathway potentially enhances fibrin deposition in an atherogenic arterial in vivo thrombosis model, which suggests a role for CD36 and ERK5 in thrombosis and coagulation in dyslipidemic conditions. DisclosuresNo relevant conflicts of interest to declare.

Study of Lipid Profile and Carcinoembryonic Antigen in Breast Cancer Patients

ABSTRACT Aim The purpose of this study was to evaluate the levels of carcinoembryonic antigen (CEA) and lipid profile [total cholesterol (TC), serum triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL)] in patients with breast cancer and compared them with healthy individuals as a control group. Materials and methods In the present study, 100 women included 50 breast cancer patients with age &gt;18 years and 50 controls with similar age range were assessed for CEA and lipid profile. Result The present study has demonstrated that the levels of CEA, TC, LDL, VLDL, and TG were significantly higher and the levels of HDL were lower in patients with breast cancer. Conclusion The study concluded that CEA levels were higher in the case group and it is one of the most commonly expressed biological markers in breast cancer patients and when lipid profile was compared between breast cancer patients and the control group, then, TC, LDL, VLDL, and TG were significantly higher and the levels of HDL were lower in patients with breast cancer. How to cite this article Sharma A, Akhtar S, Fiza B, et al. Study of Lipid Profile and Carcinoembryonic Antigen in Breast Cancer Patients. J Mahatma Gandhi Univ Med Sci Tech 2020;5(1):1–3.

Effect of vitamin E on low density lipoprotein oxidation at lysosomal pH

Many cholesterol-laden foam cells in atherosclerotic lesions are macrophages and much of their cholesterol is present in their lysosomes and derived from low density lipoprotein (LDL). LDL oxidation has been proposed to be involved in the pathogenesis of atherosclerosis. We have shown previously that LDL can be oxidised in the lysosomes of macrophages. α-Tocopherol has been shown to inhibit LDL oxidation in vitro, but did not protect against cardiovascular disease in large clinical trials. We have therefore investigated the effect of α-tocopherol on LDL oxidation at lysosomal pH (about pH 4.5). LDL was enriched with α-tocopherol by incubating human plasma with α-tocopherol followed by LDL isolation by ultracentrifugation. The α-tocopherol content of LDL was increased from 14.4 ± 0.2 to 24.3 ± 0.3 nmol/mg protein. LDL oxidation was assessed by measuring the formation of conjugated dienes at 234 nm and oxidised lipids (cholesteryl linoleate hydroperoxide and 7-ketocholesterol) by HPLC. As expected, LDL enriched with α-tocopherol was oxidised more slowly than control LDL by Cu2+ at pH 7.4, but was not protected against oxidation by Cu2+ or Fe3+ or a low concentration of Fe2+ at pH 4.5 (it was sometimes oxidised faster by α-tocopherol with Cu2+ or Fe3+ at pH 4.5). α-Tocopherol-enriched LDL reduced Cu2+ and Fe3+ into the more pro-oxidant Cu+ and Fe2+ faster than did control LDL at pH 4.5. These findings might help to explain why the large clinical trials of α-tocopherol did not protect against cardiovascular disease.

ApoF knockdown increases cholesteryl ester transfer to LDL and impairs cholesterol clearance in fat-fed hamsters

Cholesteryl ester transfer protein (CETP) regulates intravascular lipoprotein metabolism. In vitro studies indicate that ApoF alters CETP function by inhibiting its activity with LDL. To explore in vivo the complexities driving ApoF's effects on CETP, we developed a siRNA-based hamster model of ApoF knockdown. In both male and female hamsters on chow- or fat-fed diets, we measured lipoprotein levels and composition, determined CETP-mediated transfer of cholesteryl esters (CEs) between lipoproteins, and quantified reverse cholesterol transport (RCT). We found that apoF knockdown in chow-fed hamsters had no effect on lipoprotein levels or composition, but these ApoF-deficient lipoproteins supported 50-100% higher LDL CETP activity in vitro. ApoF knockdown in fat-fed male hamsters created a phenotype in which endogenous CETP-mediated CE transfer from HDL to LDL increased up to 2-fold, LDL cholesterol increased 40%, HDL declined 25%, LDL and HDL lipid compositions were altered, and hepatic LDLR gene expression was decreased. Diet-induced hypercholesterolemia obscured this phenotype on occasion. In fat-fed female hamsters, ApoF knockdown caused similar but smaller changes in plasma CETP activity and LDL cholesterol. Notably, ApoF knockdown impaired HDL RCT in fat-fed hamsters but increased sterol excretion in chow-fed animals. These in vivo data validate in vitro findings that ApoF regulates lipid transfer to LDL. The consequences of ApoF knockdown on lipoproteins and sterol excretion depend on the underlying lipid status. By minimizing the transfer of HDL-derived CE to LDL, ApoF helps control LDL cholesterol levels when LDL clearance mechanisms are limiting.

Increased retention of LDL from type 1 diabetic patients in atherosclerosis-prone areas of the murine arterial wall

Background and aimsType 1 diabetes accelerates the development of atherosclerotic cardiovascular diseases. Retention of low-density lipoprotein (LDL) in the arterial wall is a causal step in atherogenesis, but it is unknown whether diabetes alters the propensity of LDL for retention. The present study investigated whether LDL from type 1 diabetic and healthy non-diabetic subjects differed in their ability to bind to the arterial wall in a type 1 diabetic mouse model. MethodsFluorescently-labeled LDL obtained from type 1 diabetic patients or healthy controls was injected into mice with type 1 diabetes. The amount of retained LDL in the atherosclerosis-prone inner curvature of the aortic arch was quantified by fluorescence microscopy. Healthy control LDL was in vitro glycated, analyzed for protein glycation by LC-MS/MS, and tested for retention propensity. ResultsRetention of LDL from type 1 diabetic patients was 4.35-fold higher compared to LDL from nondiabetic subjects. Nuclear magnetic resonance (NMR) spectroscopy analysis of LDL revealed no differences in the concentration of the atherogenic small dense LDL between type 1 diabetic and non-diabetic subjects. In vitro glycation of LDL from a non-diabetic subject increased retention compared to non-glycated LDL. LC-MS/MS revealed four new glycated spots in the protein sequence of ApoB of in vitro glycated LDL. ConclusionsLDL from type 1 diabetic patients showed increased retention at atherosclerosis-prone sites in the arterial wall of diabetic mice. Glycation of LDL is one modification that may increase retention, but other, yet unknown, mechanisms are also likely to contribute.

Effect of high fat ketogenic diet on some cardiovascular and renal parameters in Wistar albino rats

Ketogenic diet is used in weight control. This study aimed at determining the effect of the consumption of this high fat, low carbohydrate diet on plasma viscosity, lipid profile, serum and urine creatinine, urea, electrolytes and urinary pH. Forty Wistar rats grouped into experimental (A) and control groups (B) were used. Experimental group was fed with 65% fatty diet; control group was fed with normal rat chow for eight weeks. Fasting samples were collected at the end of the study for analysis. Biochemical analyses were done using spectrophotometric method, electrolytes were assayed by the ion electrode selective method, plasma viscosity was analysed using the Reid and Ugwu method and urinalysis strip was used to measure urinary pH. A significant increase in serum (0.866±0.031) and urinary (5.470±0.424) creatinine urinary sodium (147.3±23.60), chloride (136.0±23.90), bicarbonate (1570±1065) and pH (7.60±1.63) were observed in the experimental group when compared with serum values of control group (0.6600±0.060) and urinary (1.700±0.230) creatinine, sodium (35.60±18.92), chloride (30±17.05), bicarbonate (800±184.4) and pH (6.8±0.3). A significant decrease in total cholesterol (95.60±2.64) and LDL Cholesterol (43.60±2.16) concentrations were observed in the experimental group when compared with the control group, total cholesterol (132.8±10.7) and LDL Cholesterol (69.00±10.80). This study also showed a significant increase in weight of control groups (initial weight (g) 135.2±5.115, final weight, 151.2±38.3) while there was no significant increase in weight of the experimental group (Initial weight 170.6±11.95, final weight170.6±11.21). There was no significant difference in the other parameters when both groups were compared. These findings have clearly shown that intake of high fat ketogenic diet is not harmful to the heart, however the increase in serum creatinine in the experimental group could be as a result of the effect of the diet on the kidney or it could be due to muscle wastage which might be responsible for maintenance of their body weight. Increased urinary sodium excretion could lead to increased loss of fluid which can also give an impression of weight loss. © 2018 International Formulae Group. All rights reserved. Keywords: Ketogenic diet, Cardiovascular, Renal, plasma viscosity, lipid profile, electrolytes