scholarly journals Plasma PCSK9 Concentrations Correlate with LDL and Total Cholesterol in Diabetic Patients and Are Decreased by Fenofibrate Treatment

2008 ◽  
Vol 54 (6) ◽  
pp. 1038-1045 ◽  
Author(s):  
Gilles Lambert ◽  
Nicolas Ancellin ◽  
Francesca Charlton ◽  
Daniel Comas ◽  
Julia Pilot ◽  
...  
Keyword(s):  
Ldl Cholesterol ◽  
Polyclonal Antibodies ◽  
Sandwich Elisa ◽  
Ldl Receptor ◽  
Hdl Cholesterol ◽  
Diabetic Patients ◽  
Plasma Triglycerides ◽  
Fenofibrate Treatment ◽  
Before And After ◽  
Fenofibrate Intervention

Abstract Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of the LDL receptor (LDLr) in hepatocytes, and its expression in mouse liver has been shown to decrease with fenofibrate treatment. Methods: We developed a sandwich ELISA using recombinant human PCSK9 protein and 2 affinity-purified polyclonal antibodies directed against human PCSK9. We measured circulating PCSK9 concentrations in 115 diabetic patients from the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) study before and after fenofibrate treatment. Results: We found that plasma PCSK9 concentrations correlate with total (r = 0.45, P = 0.006) and LDL (r = 0.54, P = 0.001) cholesterol but not with triglycerides or HDL cholesterol concentrations in that cohort. After 6 weeks of treatment with comicronized fenofibrate (200 mg/day), plasma PCSK9 concentrations decreased by 8.5% (P = 0.041 vs pretreatment). This decrease correlated with the efficacy of fenofibrate, as judged by a parallel reduction in plasma triglycerides (r = 0.31, P = 0.015) and LDL cholesterol concentrations (r = 0.27, P = 0.048). Conclusions: We conclude that this decrease in PCSK9 explains at least in part the LDL cholesterol–lowering effects of fenofibrate. Fenofibrate might be of interest to further reduce cardiovascular risk in patients already treated with a statin.

scholarly journals Familial Hypercholesterolemia: Three “under” (Understood, Underdiagnosed, and Undertreated) Disease

2021 ◽  
Author(s):  
Vladimir O. Konstantinov
Keyword(s):  
Familial Hypercholesterolemia ◽  
Time Course ◽  
Ldl Cholesterol ◽  
Genetic Disorders ◽  
Receptor Gene ◽  
Ldl Receptor ◽  
Hdl Cholesterol ◽  
Blood Cholesterol ◽  
Healthy Population ◽  
Loss Of Function

Familial hypercholesterolemia (FH) is one of the most prevalent genetic disorders leading to premature atherosclerosis and coronary heart disease. The main cause of FH is a mutation in the LDL-receptor gene that leads to loss of function of these receptors causing high levels of blood cholesterol. The diagnosis of FH is not very easy. Wide screenings are needed to reveal high levels of LDL cholesterol among “healthy” population. If the patient has MI or stroke at an early age, high levels of LDL cholesterol, and tendon xanthomas, the diagnosis of FH becomes much more clear. Genetic testing is a gold standard in the diagnosis of FH. There are several factors, influencing the time course of FH. Smoking males with low levels of HDL cholesterol have an extremely higher risk of death than nonsmoking females with high HDL cholesterol. Management of FH includes low cholesterol diet, statin and ezetimibe treatment, PCSK inhibitors, and LDL aphaeresis. Early and effective treatment influences much the prognosis in FH patients.

scholarly journals FXR activation by obeticholic acid or nonsteroidal agonists induces a human-like lipoprotein cholesterol change in mice with humanized chimeric liver

2018 ◽  
Vol 59 (6) ◽  
pp. 982-993 ◽  
Author(s):  
Romeo Papazyan ◽  
Xueqing Liu ◽  
Jingwen Liu ◽  
Bin Dong ◽  
Emily M. Plummer ◽  
...  
Keyword(s):  
Target Gene ◽  
Ldl Cholesterol ◽  
Ldl Receptor ◽  
Hdl Cholesterol ◽  
Farnesoid X Receptor ◽  
Receptor Protein ◽  
Chimeric Mice ◽  
Obeticholic Acid ◽  
Protein Levels ◽  
Mechanistic Basis

Obeticholic acid (OCA) is a selective farnesoid X receptor (FXR) agonist that regulates bile acid and lipid metabolism. FXR activation induces distinct changes in circulating cholesterol among animal models and humans. The mechanistic basis of these effects has been elusive because of difficulties in studying lipoprotein homeostasis in mice, which predominantly package circulating cholesterol in HDLs. Here, we tested the effects of OCA in chimeric mice whose livers are mostly composed (≥80%) of human hepatocytes. Chimeric mice exhibited a human-like ratio of serum LDL cholesterol (LDL-C) to HDL cholesterol (HDL-C) at baseline. OCA treatment in chimeric mice increased circulating LDL-C and decreased circulating HDL-C levels, demonstrating that these mice closely model the cholesterol effects of FXR activation in humans. Mechanistically, OCA treatment increased hepatic cholesterol in chimeric mice but not in control mice. This increase correlated with decreased SREBP-2 activity and target gene expression, including a significant reduction in LDL receptor protein. Cotreatment with atorvastatin reduced total cholesterol, rescued LDL receptor protein levels, and normalized serum LDL-C. Treatment with two clinically relevant nonsteroidal FXR agonists elicited similar lipoprotein and hepatic changes in chimeric mice, suggesting that the increase in circulating LDL-C is a class effect of FXR activation.

scholarly journals Human cholesteryl ester transfer protein measured by enzyme-linked immunosorbent assay with two monoclonal antibodies against rabbit cholesteryl ester transfer protein: plasma cholesteryl ester transfer protein and lipoproteins among Japanese hypercholesterolemic patients

1998 ◽  
Vol 44 (7) ◽  
pp. 1466-1473 ◽  
Author(s):  
Kanna Sasai ◽  
Kuniko Okumura-Noji ◽  
Takeshi Hibino ◽  
Reiko Ikeuchi ◽  
Nagahiko Sakuma ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Cholesteryl Ester ◽  
Cholesteryl Ester Transfer Protein ◽  
Ldl Cholesterol ◽  
Hdl Cholesterol ◽  
Enzyme Linked Immunosorbent Assay ◽  
Transfer Protein ◽  
Plasma Cholesteryl Ester ◽  
Luminal Stenosis ◽  
Before And After

Abstract Plasma cholesteryl ester transfer protein (CETP) concentrations were measured in Japanese subjects by an ELISA with two different monoclonal antibodies that were raised against rabbit CETP and cross-reacted against human CETP. Among 63 patients who consecutively underwent coronary angiography, the plasma CETP of 37 patients with luminal stenosis ≥50% in their coronary arteries was not significantly different from that of the 26 patients with luminal stenosis <50%. No other lipoprotein-related measurement except HDL-cholesterol differentiated the two groups. Among 40 hypercholesterolemic patients, no lipoprotein-related measurement other than LDL-cholesterol was found to positive correlate with the CETP. Before and after the treatment of 23 patients with simvastatin 5 mg a day for 4 weeks, plasma CETP markedly decreased in those whose pretreatment CETP was ≥3 mg/L; no change was observed for those with lower pretreatment CETP. In the former group, negative correlation between CETP and HDL-cholesterol was demonstrated only in the posttreatment plasma.

scholarly journals Pengaruh propolis terhadap profil lipid plasma tikus model hiperkolesterolemia

2012 ◽  
Vol 8 (3) ◽  
pp. 106
Author(s):  
Krisnansari Diah ◽  
Ariadne Tiara Hapsari ◽  
Evy Sulistyoningrum ◽  
Agus Prastowo
Keyword(s):  
Lipid Profile ◽  
Total Cholesterol ◽  
Ldl Cholesterol ◽  
Plasma Cholesterol ◽  
Hdl Cholesterol ◽  
Sprague Dawley ◽  
High Cholesterol ◽  
Cholesterol Levels ◽  
Group I ◽  
Before And After

Background: Nowadays, cardiovascular disease caused by hypercholesterolemia has become the main cause of death. Propolis has been used widely to reduce plasma cholesterol levels.Objective: The aims of this research was to study the effect of propolis on lipid profile of hypercholesterolemic Sprague Dawley rats.Method: This was an experimental study with pre-post test. Twenty four (24) male Sprague Dawley rats aged 12-16 week old, weighing 125-200 g were allocated into 4 groups. Group I received standard meal + aquadest-gavage; group II received high cholesterol meal + PTU 0,01 + aquadest gavage; group III received high cholesterol meal + PTU 0,01 + 0,027 g propolis gavage; group IV received high cholesterol meal + PTU 0,01 + 0,054 g propolis gavage. Total cholesterol, triglycerides, HDL cholesterol and LDL cholesterol levels before and after treatment were measured. The data were then analyzed with One Way Anova.Results: The study showed that there were no significant differences in changes of body weight. There were significant differences in total cholesterol levels between all groups of treatment. Triglyceride levels were significantly different among all groups, except between group I and IV. Furthermore, the HDL cholesterol levels of group I vs III and group I vs IV were significantly different. However, there were no differences found in LDL cholesterol levels among all groups of treatment.Conclusion: Provision of 0,027 g and 0,054 g propolis improve lipid profile (total cholesterol, triglyceride and HDL cholesterol levels) of hypercholesterolemic rats.

scholarly journals The role of plant stanols in the primary prevention of hypercholesterolemia in patients with arterial hypertension

2019 ◽  
Vol 18 (3) ◽  
pp. 5-10
Author(s):  
A. S. Safaryan ◽  
T. V. Kamyshova ◽  
D. V. Nebieridze ◽  
V. D. Sargsyan
Keyword(s):  
Total Cholesterol ◽  
Ldl Cholesterol ◽  
Clinical Manifestations ◽  
Hdl Cholesterol ◽  
Average Level ◽  
Control Group ◽  
Study Group ◽  
Plant Stanols ◽  
Before And After ◽  
Lipid Parameters

Aim. To assess the efficacy and safety of plant stanols in patients with arterial hypertension (AH) and disorders of lipid metabolism, without clinical manifestations of atherosclerosis.Material and methods. The study included 40 patients — men at the age of 50-55 years, with AH (stage 1) and cholesterol above 5,0 mmol/l and LDL cholesterol above 3,0 mmol/l with low and medium risk (SCORE — 1-4%). Patients with coronary artery disease and other clinical manifestations of atherosclerosis, secondary hypertension, liver diseases, diabetes mellitus, secondary dyslipoproteinemia, cardiovascular diseases requiring constant therapy, bronchial asthma were excluded from the study. Patients were randomized into 2 groups of 20 people. In the study group of patients within 3 months received plant stanols (2 tab./day), in the control group — only healthy diet. In addition, patients with high blood pressure received antihypertensive therapy. Assessment of lipid parameters (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides) was performed at baseline and after 3 months. At the beginning of the study, after 3 months of the study patients underwent a full medical examination. Safety control of plant stanols was carried out by determination of liver enzymes (aspartic transaminase (AST), alanine transaminase (ALT)), before and after the completion of the study.Results. Patients of two groups were comparable in baseline characteristics (lipid parameters, blood pressure level). After 3 months of research beginning patients from study group have statistically significant decrease of total cholesterol and LDL cholesterol. The average level of total cholesterol before treatment was 5,8±0,32 mmol/l, and after treatment — 5,3±0,32 mmol/l, p<0,001. The average level of LDL cholesterol before treatment was 3,6±0,26 mmol/l, and after treatment — 3,3±0,25 mmol/l, p<0,001. According to other lipid parameters (HDL cholesterol, triglycerides) significant differences are not obtained. As a result, there was a significant reduction in the total risk from 4% to 3,1%. As for the control group, the dynamics of lipid parameters were practically not observed. For example, the average level of total cholesterol before treatment was 5,7±0,39 mmol/l, and after treatment — 5,6±0,42 mmol/l. The average level of LDL cholesterol before treatment was 3,6±0,21 mmol/l, and after treatment — 3,6±0,21 mmol/l. The differences between the study and control groups in the reduction of total and LDL cholesterol were highly significant (p<0,001). The study did not reveal the dynamics of liver enzymes. The level of AST before treatment in the study group was 28,4±6,54, and after treatment — 29,5±5,56. ALT levels were 32,3±7,38 and 33,9±5,65, before and after the study, respectively.Conclusion. The study shows the high efficacy and safety of plant stanols. We found a significant decrease of the two most important parameters of lipid metabolism — total cholesterol and LDL cholesterol.

scholarly journals Glycated Hemoglobin and Lipid Profile Association Among Pregnant Women in Saudi Arabian Population

2018 ◽  
Vol 7 (2) ◽  
pp. 216-222
Author(s):  
Farah Anjum ◽  
Rana Zaini ◽  
Ashjan Shami ◽  
Amani Rehaili ◽  
Rahma Kufia
Keyword(s):  
Pregnant Women ◽  
Lipid Profile ◽  
Ldl Cholesterol ◽  
Glycated Hemoglobin ◽  
Previous History ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Oral Glucose ◽  
Diabetic Patients ◽  
Significant Difference

Objectives: Glycated hemoglobin (HbA1c) is the most commonly used glycemic index among diabetic patients. The present study sought to investigate the relationship between HbA1c and lipid parameters among healthy pregnancies and gestational diabetic cases. Materials and Methods: Seventy-five Saudi pregnant women within the age group of 19 to 43 years were selected for this crosssectional study. The participants were categorized into with and without gestational diabetes (GDM), all of whom were non-smokers; in addition, they neither had a previous history of chronic illnesses nor were they on any medications which could alter lipid profile and HbA1c concentrations. Totally, 75 g of oral glucose tolerance test (OGTT) was utilized to identify 25 women with GDM. All biochemical tests including HbA1c, fasting blood sugar (FBG), total cholesterol (TC), low-density lipoprotein (LDL-cholesterol), triglycerides (TG), and high-density lipoprotein (HDL-cholesterol) were performed by a biochemical auto-analyzer. The collected data were statistically analyzed using a paired student’s t test. The P values of <0.05 were considered statistically significant on all the analyses related to healthy pregnancies and those associated with GDM. Results: The HbA1c and FBG values demonstrated significant correlation with GDM (P<0.001 each). However, TC, LDL-cholesterol, and TG failed to indicate any significant difference between the 2 groups. Conversely, HDL-cholesterol and the ratio of TG and HDLcholesterol revealed remarkable differences between GDM and healthy participants (P<0.05 each). Conclusions: In general, the blood levels of glucose, HbA1c, TG, and HDL-cholesterol are of paramount significance in GDM. Predictably, HbA1c can be employed as one of the markers in evaluating the risk factors in developing dyslipidemia among pregnant women.

scholarly journals Dairy calcium intake modifies responsiveness of fat metabolism and blood lipids to a high-fat diet

2011 ◽  
Vol 105 (12) ◽  
pp. 1823-1831 ◽  
Author(s):  
Janne K. Lorenzen ◽  
Arne Astrup
Keyword(s):  
Dairy Products ◽  
Ldl Cholesterol ◽  
Saturated Fat ◽  
Hdl Cholesterol ◽  
Fat Intake ◽  
High Fat ◽  
Dairy Fat ◽  
Before And After ◽  
Fat Excretion ◽  
Blood Variables

Intervention studies have demonstrated that saturated fat increases total and LDL-cholesterol concentrations, and it is therefore recommended that the intake of high-fat dairy products be limited. However, observational studies have found an inverse relationship between the intake of dairy products and incidence of CVD. We aimed to study whether the Ca content of dairy products influences the effect of dairy fat on the lipid profile. The study had a randomised cross-over design. Subjects (n9) were randomised to one of the sequence of four isoenergetic 10 d diets: low Ca and low fat (LC/LF: approximately 700 mg Ca/d, 25 % of energy (fat); high Ca and LF (HC/LF: approximately 2800 mg Ca/d, 25 % of energy fat); LC and high fat (LC/HF: approximately 700 mg Ca/d, 49 E% fat); or HC and HF (approximately 2800 mg Ca/d, 49 E% fat). Blood variables were measured before and after each diet period, and faeces and urine were collected at the end of each diet period. A two-way ANOVA was used to examine the effect of Ca and fat intake. Independent of Ca intake, the HF diet increased the concentrations of total (9 %;P < 0·0001), LDL (14 %;P < 0·0001)- and HDL (13 %;P = 0·0002)-cholesterol compared with the LF diet. However, independent of fat intake, the HC diet decreased the concentrations of total (4 %;P = 0·0051) and LDL-cholesterol (10 %;P < 0·0001) but not HDL-cholesterol compared with the LC diet. In addition, total:HDL-cholesterol was decreased (5 %;P = 0·0299), and HDL:LDL was increased (12 %;P = 0·0097) by the HC diet compared with the LC diet. Faecal fat excretion was increased by both the HC (P < 0·0001) and HF (P = 0·0052) diets. In conclusion, we observed that dairy Ca seems to partly counteract the raising effect of dairy fat on total and LDL-cholesterol, without reducing HDL-cholesterol.

scholarly journals Plasmapheresis for Spur Cell Anemia in a Patient with Alcoholic Liver Cirrhosis

2018 ◽  
Vol 2018 ◽  
pp. 1-4 ◽  
Author(s):  
Kenji Miki ◽  
Takashi Maruki ◽  
Shinsaku Imashuku
Keyword(s):  
Liver Cirrhosis ◽  
Serum Lipid ◽  
Free Cholesterol ◽  
Ldl Cholesterol ◽  
Hdl Cholesterol ◽  
Alcoholic Liver Cirrhosis ◽  
Red Cell ◽  
Before And After ◽  
Old Japanese ◽  
Previously Treated

Background. Spur cell anemia (SCA) is a cause of hemolytic anemia in patients with alcoholic liver cirrhosis. Because dyslipidemia is related to the development of spur cells, SCA was previously treated with plasmapheresis. Case Report. A 52-year-old Japanese man with SCA associated with alcoholic liver cirrhosis (Child–Pugh C) underwent two rounds of plasmapheresis. Clinical features and serum lipid concentrations were compared before and after plasmapheresis. Although indirect hyperbilirubinemia and SCA persisted after plasmapheresis, reticulocyte counts significantly decreased from 22.4% to 4.5%, and Hb levels improved without red cell transfusions. Analysis of lipids showed that total and free cholesterol, HDL cholesterol, phospholipid, and apo-AI concentrations, all of which were reduced before plasmapheresis, had improved after treatment, while LDL cholesterol, lipoprotein (a), and apo-AII concentrations, which were also reduced before plasmapheresis, remained unchanged. Conclusions. Despite plasmapheresis partially ameliorating the degree of hemolysis, the persistence of SCA may have been linked with the lack of improvement in certain types of lipid metabolism.

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