scholarly journals The Association of Proprotein Convertase Subtilisin/Kexin Type 9 to Plasma Low-Density Lipoproteins: An Evaluation of Different Methods

Metabolites ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 861
Author(s):  
Laura Canclini ◽  
Amir Mohammad Malvandi ◽  
Patrizia Uboldi ◽  
Najoua Jabnati ◽  
Liliana Grigore ◽  
...  
Keyword(s):  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Significant Proportion ◽  
Density Lipoprotein ◽  
Low Density Lipoproteins ◽  
High Salt ◽  
Low Density ◽  
Proprotein Convertase ◽  
Cholesterol Levels ◽  
Lower Size

Background: Proprotein convertase subtilisin/kexin type-9 (PCSK9) is key regulator of low-density lipoprotein (LDL) metabolism. A significant proportion of PCSK9 is believed to be associated with LDL in plasma as it circulates, although this finding is still a matter of debate. The purpose of this study was to establish an experimental method to investigate the presence of such an interaction in the bloodstream. Methods: We compared a number of well-established methods for lipoprotein (LP) isolation to clarify whether PCSK9 associates differently to circulating lipoproteins, such as KBr gradient ultracentrifugation, physical precipitation of ApoB-LPs, fast protein liquid chromatography (FPLC) and iodixanol gradient ultracentrifugation. Results: Our data show heterogeneity in PCSK9 association to lipoproteins according to the method used. Two methods, iodixanol ultracentrifugation and column chromatography, which did not involve precipitation or high salt concentration, consistently showed an interaction of PCSK9 with a subfraction of LDL that appeared to be more buoyant and have a lower size than average LDL. The percent of PCSK9 association ranged from 2 to 30% and did not appear to correlate to plasma or LDL cholesterol levels. Conclusions: The association of PCSK9 to LDL appeared to be sensitive to high salt concentrations. FPLC and iodixanol gradient ultracentrifugation appeared to be the most suitable methods for the study of this association.

scholarly journals Proprotein Convertase Subtilisin/Kexin Type 9: From the Discovery to the Development of New Therapies for Cardiovascular Diseases

Scientifica ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-21 ◽  
Author(s):  
Nicola Ferri
Keyword(s):  
Cardiovascular Diseases ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Homeostasis ◽  
Low Density ◽  
Regulatory Effect ◽  
Proprotein Convertase ◽  
Pharmacological Modulation ◽  
Cholesterol Levels

The identification of the HMG-CoA reductase inhibitors, statins, has represented a dramatic innovation of the pharmacological modulation of hypercholesterolemia and associated cardiovascular diseases. However, not all patients receiving statins achieve guideline-recommended low density lipoprotein (LDL) cholesterol goals, particularly those at high risk. There remains, therefore, an unmet medical need to develop additional well-tolerated and effective agents to lower LDL cholesterol levels. The discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9), a secretory protein that posttranscriptionally regulates levels of low density lipoprotein receptor (LDLR) by inducing its degradation, has opened a new era of pharmacological modulation of cholesterol homeostasis. This paper summarizes the current knowledge of the basic molecular mechanism underlying the regulatory effect of LDLR expression by PCSK9 obtained fromin vitrocell-cultured studies and the analysis of the crystal structure of PCSK9. It also describes the epidemiological and experimental evidences of the regulatory effect of PCSK9 on LDL cholesterol levels and cardiovascular diseases and summarizes the different pharmacological approaches under development for inhibiting PCSK9 expression, processing, and the interaction with LDLR.

Abstract P307: Chitin-Glucan Fiber Effects on Oxidized Low-Density Lipoprotein: A Randomized Controlled Trial

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Joseph L Evans ◽  
Harold Bays ◽  
Kevin C Maki ◽  
Mal Evans ◽  
Veronique Maquet ◽  
...  
Keyword(s):  
Diabetes Complications ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Secondary Outcome ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Treatment Groups ◽  
Cholesterol Levels ◽  
Insoluble Fiber

Oxidized low-density lipoprotein (OxLDL) is believed to play a role in the progression of atherosclerotic coronary heart disease (CHD) and the development of diabetes complications. This randomized, double-blind, placebo-controlled study of a novel insoluble fiber derived from the mycelium Aspergillus niger , chitin-glucan (CG) (ARTINIA™), evaluated 135 patients with fasting LDL-cholesterol 130-189.9 mg/dl and fasting glucose <=125 mg/dl. Participants were randomly assigned to receive CG (4.5 g/day; n=34), CG (1.5 g/day; n=33), CG (1.5 g/day) plus olive extract (n=33), or matching placebo (n=35) for 6 weeks. The primary outcome measure was the between-group difference in OxLDL. Secondary outcome measurements included effects upon lipid, glucose, insulin, and F2-isoprostane levels. After 6 weeks, CG 4.5 g/day (CG-4.5) significantly reduced mean OxLDL 3.8 U/L compared to baseline (58.0 U/L vs 61.8 U/L, respectively; P =0.006), and reduced OxLDL 4.97 U/L compared to placebo (P=<0.05). Other treatment groups generally had no significant effect upon OxLDL. CG treatment groups reduced LDL-cholesterol levels 3.2–;6.5% compared to placebo (P<0.05). In this study population without diabetes mellitus or elevated glucose levels, CG did not significantly affect high density lipoprotein cholesterol, triglycerides, glucose, insulin, F2-isoprostanes, or the homeostasis model assessment of insulin resistance. Treatments were well tolerated and with adverse experiences comparable to placebo. These results suggest that chitin-glucan, a novel insoluble fiber, may significantly reduce OxLDL and LDL-cholesterol levels, which may have therapeutic implications for patients at risk for CHD or other diabetes complications.

Secondary prevention care and effect: Total and low-density lipoprotein cholesterol levels and lipid-lowering drug use in women and men after incident myocardial infarction – The Tromsø Study 1994–2016

2018 ◽  
Vol 17 (6) ◽  
pp. 563-570 ◽  
Author(s):  
Laila A Hopstock ◽  
Anne Elise Eggen ◽  
Maja-Lisa Løchen ◽  
Ellisiv B Mathiesen ◽  
Inger Njølstad ◽  
...  
Keyword(s):  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Low Density ◽  
Lipid Levels ◽  
Treatment Target ◽  
Cholesterol Levels ◽  
Lipid Lowering Drug ◽  
Lowering Drug

Background: Secondary prevention guidelines after myocardial infarction (MI) are gender neutral, but underutilisation of treatment in women has been reported. Design: We investigated the change in total and low-density lipoprotein (LDL) cholesterol levels and lipid-lowering drug (LLD) use after first-ever MI in a population-based study. Methods: We followed 10,005 participants (54% women) attending the Tromsø Study 1994–1995 and 8483 participants (55% women) attending the Tromsø Study 2007–2008 for first-ever MI up to their participation in 2007–2008 and 2015–2016, respectively. We used linear and logistic regression models to investigate sex differences in change in lipid levels. Results: A total of 395 (MI cohort I) and 132 participants (MI cohort II) had a first-ever MI during 1994–2008 and 2007–2013, respectively. Mean change in total cholesterol was −2.34 mmol/L (SD 1.15) in MI cohort I, and in LDL cholesterol was −1.63 mmol/L (SD 1.12) in MI cohort II. Men had a larger decrease in lipid levels compared to women: the linear regression coefficient for change was −0.33 (95% confidence interval [CI] −0.51 to −0.14) for total cholesterol and −0.21 (95% CI −0.37 to −0.04) for LDL cholesterol, adjusted for baseline lipid value, age and cohort. Men had 73% higher odds (95% CI 1.15−2.61) of treatment target achievement compared to women, adjusted for baseline lipid value, age and cohort. LLD use was reported in 85% of women and 92% of men in MI cohort I, and 80% in women and 89% in men in MI cohort II. Conclusions: Compared to men, women had significantly less decrease in lipid levels after MI, and a smaller proportion of women achieved the treatment target.

scholarly journals The Description of Low Density Lipoprotein (LDL) Levels on Smoker and Non Smoker Adolescent in Buyan Hamlet, Pancasari Village, Sukasada District, Buleleng, Bali

2017 ◽  
Vol 4 (1) ◽  
pp. 39-44
Author(s):  
Ni Made Restina Juliani ◽  
I Putu Oka Dharmawan ◽  
Putu Ayu Parwati
Keyword(s):  
Physical Activity ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
The Body ◽  
Low Density ◽  
Blood Samples ◽  
Cholesterol Levels

Introduction: Low Density Lipoprotein (LDL) is a type of low-density lipoprotein and the most widely transported cholesterol in the body. Increased levels of LDL in the body can be affected by genetics, age, gender, obesity, physical activity, lifestyle, drug consumption and smoking. Substances in a cigarette can cause an increase of LDL levels. Increased of LDL cholesterol levels can cause Coronary Heart Disease (CHD). The purpose of this research is to know the description of Low Density Lipoprotein (LDL) levels on smoker and non-smoker adolescent in Buyan Hamlet, Pancasari Village, Sukasada District, Buleleng Bali. Method: The type of this research is descriptive. This research was conducted in April-May 2017, which used fasting blood samples of 42 respondents. Result: From the average result of LDL level in smoker adolescent that is 134,91 mg/dL higher than the average of LDL level in non-smoker adolescent that is 74,90 mg/dL. The result of LDL cholesterol levels was determined by 21 smoker adolescent respondents with the close to optimal category (100-129 mg/dL) as many as 9 people (42,8%), and 12 people (57,3%) with worry category (130-159 mg/dL). Whereas in 21 non-smoker adolescent respondents obtained  result of LDL cholesterol level test with optimal category (<100 mg/dL) counted 18 people (87,71%) and 3 person (14,30%) with close to optimal category (100-129 mg/dL). Discussion: Based on the results of this research can be concluded that in smoker adolescent obtained LDL levels with close to optimal category and worrying whereas in non-smoker adolescents obtained LDL levels in the optimal category and close to optimal.

Bezafibrate

1983 ◽  
Vol 21 (19) ◽  
pp. 75-76
Keyword(s):  
High Density Lipoprotein ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Significant Risk ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Lipid Lowering ◽  
Low Density ◽  
Cholesterol Levels ◽  
The Uk

Bezafibrate (Bezalip - MCP), an analogue of clofibrate (Atromid-S), has been marketed in the UK for two years. Like clofibrate 1 it lowers both triglyceride and total cholesterol levels in plasma. The reduction is usually in low-density lipoprotein (LDL) cholesterol, whilst high-density lipoprotein (HDL) cholesterol rises. Like other lipid-lowering drugs, it should be used only where appropriate dietary measures have failed and where the hyperlipidaemia poses a significant risk.2

Cigarette Smoking-Associated Changes in Blood Lipid and Lipoprotein Levels in the 8-to 19-Year-Old Age Group: A Meta-Analysis

PEDIATRICS ◽  
1990 ◽  
Vol 85 (2) ◽  
pp. 155-158
Author(s):  
Wendy Y. Craig ◽  
Glenn E. Palomaki ◽  
A. Myron Johnson ◽  
James E. Haddow
Keyword(s):  
Total Cholesterol ◽  
Old Age ◽  
Ldl Cholesterol ◽  
Meta Analysis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Low Density ◽  
Age Group ◽  
Cholesterol Levels

In this meta-analysis it was demonstrated that, when compared with nonsmokers of similar age, smokers in the 8- to 19-year-old age group have significantly higher serum levels of triglyceride (+11.8%), very-low-density lipoprotein (VLDL)-cholesterol (+12.4%) and low-density lipoprotein (LDL)-cholesterol (+4.1%) and significantly lower serum levels of high-density lipoprotein (HDL)-cholesterol (-8.5%) and total cholesterol (-3.7%). All of these smoking-associated changes are in the same direction as those found in adults, with the exception of total cholesterol levels, which are significantly increased in adult smokers. The extent to which mean triglyceride, LDL-cholesterol, and HDL-choles-terol levels are shifted is significantly greater in the 8-to 19-year-old smokers than in adult smokers. The changes in mean total cholesterol levels among smokers in both age groups represent only the net shifts in the lipoprotein fractions and are therefore likely to be a less sensitive indicator of the possible lipid-related excess coronary artery disease risk in smokers.

Effect of a Long-Term Fat-Modified Diet on Serum Lipoprotein Levels of Cholesterol and Triglyceride in Patients on Home Haemodialysis

1981 ◽  
Vol 60 (1) ◽  
pp. 81-86 ◽  
Author(s):  
V. J. Wass ◽  
R. J. Jarrett ◽  
V. Meilton ◽  
M. K. Start ◽  
M. Mattock ◽  
...  
Keyword(s):  
Total Cholesterol ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Low Density ◽  
Home Haemodialysis ◽  
Cholesterol Levels ◽  
Modified Diet

1. Changes in serum total and lipoprotein fraction triglyceride and cholesterol levels were studied in 24 adults on home haemodialysis. Half the patients were randomly allocated to a low cholesterol (mean 200 mg/day), fat-modified diet (mean polyunsaturated/saturated fat ratio of 1.0 with a mean of 43% of the total energy content derived from fat). 2. Before dietary manipulation, triglyceride levels in all lipoprotein fractions were significantly higher (P < 0.02) than in a control group of age and sex matched normal subjects. Total cholesterol, very-low-density-lipoprotein (VLDL) and low-density-lipoprotein (LDL) cholesterol were also significantly raised (P < 0.02), but high-density-lipoprotein (HDL) cholesterol was normal. In the patients on a fat-modified diet triglyceride levels did not alter in any of the lipoprotein fractions. Total cholesterol and LDL cholesterol levels fell significantly into the normal range (P < 0.002 and < 0.001 respectively) but VLDL and HDL cholesterol levels did not change. 3. Hypertriglyceridaemia is the most common lipid abnormality in patients with renal failure and a long-term fat-modified diet is, therefore, of limited therapeutic importance in these patients unless there is a low HDL/LDL cholesterol ratio.

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