Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression.

Background. Postmenopausal estrogen-replacement therapy may reduce the risk of cardiovascular disease, and this beneficial effect may be mediated in part by favorable changes in plasma lipid levels. However, the effects on plasma lipoprotein levels of postmenopausal estrogens in the low doses currently used have not been precisely quantified, and the mechanism of these effects is unknown. Methods. We conducted two randomized, double-blind crossover studies in healthy postmenopausal women who had normal lipid values at base line. In study 1, 31 women received placebo and conjugated estrogens at two doses (0.625 mg and 1.25 mg per day), each treatment for three months. In study 2, nine women received placebo, oral micronized estradiol (2 mg per day), and transdermal estradiol (0.1 mg twice a week), each treatment for six weeks. The metabolism of very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) was measured by endogenously labeling their protein component, apolipoprotein B. Resu...

https://www.nejm.org/doi/pdf/10.1056/NEJM199110243251702

Effects of postmenopausal estrogen replacement on the concentrations and metabolism of plasma lipoproteins.

In view of the evidence linking plasma high density lipoprotein (HDL)-cholesterol levels to a protective effect against coronary artery disease and the widespread use of fibrates in the treatment of hyperlipidemia, the goal of this study was to analyze the influence of fibrates on the expression of apolipoprotein (apo) A-II, a major protein constituent of HDL. Administration of fenofibrate (300 mg/d) to 16 patients with coronary artery disease resulted in a marked increase in plasma apo A-II concentrations (0.34 +/- 0.11 to 0.45 +/- 0.17 grams/liter; P < 0.01). This increase in plasma apo A-II was due to a direct effect on hepatic apo A-II production, since fenofibric acid induced apo A-II mRNA levels to 450 and 250% of control levels in primary cultures of human hepatocytes and in human hepatoblastoma HepG2 cells respectively. The induction in apo A-II mRNA levels was followed by an increase in apo A-II secretion in both cell culture systems. Transient transfection experiments of a reporter construct driven by the human apo A-II gene promoter indicated that fenofibrate induced apo A-II gene expression at the transcriptional level. Furthermore, several other peroxisome proliferators, such as the fibrate, Wy-14643, and the fatty acid, eicosatetraynoic acid (ETYA), also induced apo A-II gene transcription. Unilateral deletions and site-directed mutagenesis identified a sequence element located in the J-site of the apo A-II promoter mediating the responsiveness to fibrates and fatty acids. This element contains two imperfect half sites spaced by 1 oligonucleotide similar to a peroxisome proliferator responsive element (PPRE). Cotransfection assays showed that the peroxisome proliferator activated receptor (PPAR) transactivates the apo A-II promoter through this AII-PPRE. Gel retardation assays demonstrated that PPAR binds to the AII-PPRE with an affinity comparable to its binding affinity to the acyl coA oxidase (ACO)-PPRE. In conclusion, in humans fibrates increase plasma apo A-II concentrations by inducing hepatic apo A-II production. Apo A-II expression is regulated at the transcriptional level by fibrates and fatty acids via the interaction of PPAR with the AII-PPRE, thereby demonstrating the pivotal role of PPAR in controlling human lipoprotein metabolism.

/pdf/fibrates-increase-human-apolipoprotein-a-ii-expression-54y0wah6o5.pdf

Fibrates increase human apolipoprotein A-II expression through activation of the peroxisome proliferator-activated receptor.

Despite the benefits of currently available preventative and therapeutic interventions, atherosclerotic vascular disease continues to be a major cause of morbidity and mortality in much of the Western World. This emphasize,,, the need for additional preventive and therapeutic interventions exploiting new targets to compliment and augment the results of LDL lowering and other current strategies. One such potential target is HDL and its apolipoproteins, A large body of experimental evidence suggests that augmenting the levels and/or function of HDL and its apolipoproteins can have major vascular protective effects ranging from prevention to stabilization and regression, independent of total or non-HDL cholesterol levels. Therefore, we think that the time is ripe for the development and clinical testing of this new frontier in antiatherogenic strategy. In the present article, We will review the structure/function of HDL and explore means of enhancing the levels and/or function of HDL and its apolipoproteins for vascular protection. (Less)

Exploiting the Vascular Protective Effects of High-Density Lipoprotein and Its Apolipoproteins An Idea Whose Time for Testing Is Coming, Part I

Objective— High-density lipoprotein (HDL) is a heterogeneous lipoprotein class and there is no consensus on the value of HDL subspecies in coronary heart disease (CHD) risk assessment. We tested the hypothesis whether specific HDL subpopulations are significantly associated with CHD-prevalence.

Methods and Results— ApoA-I concentrations (mg/dL) in HDL subpopulations were quantitatively determined by native 2d gel electrophoresis, immunoblotting, and image analysis in male participants in the Framingham Offspring Study (FOS). CHD cases (n=169) had higher preβ-1 and α-3 particle and lower α-1, preα-3, and preα-1 particle levels than either all (n=1277) or HDL cholesterol-matched (n=358) controls. α-1 and preα-3 levels had an inverse association, whereas α-3 and preα-1 particle levels had a positive association with CHD prevalence after adjusting the data for established CHD risk factors. Standardized logit coefficients indicated that α-1 HDL was most significantly associated with CHD prevalence. Moreover, each mg/dL increase in α-1 particle level decreased odds of CHD by 26% ( P <0.0001), whereas each mg/dL increase in HDL cholesterol decreased odds of CHD by 2% in a model including all established CHD risk factors.

Conclusions— Specific HDL subpopulations were positively correlated, whereas others were inversely correlated with CHD prevalence in male subject in the FOS, indicating that the various HDL particles might have different roles in the cause of CHD.

High-Density Lipoprotein Subpopulation Profile and Coronary Heart Disease. Prevalence in Male Participants of the Framingham Offspring Study

We describe a method for measuring apolipoprotein A-I (ApoA-I) associated and unassociated with apolipoprotein A-II (ApoA-II) in plasma To directly determine associated ApoA-I, we coated microtiter plates with antibody to ApoA-II, blocked the nonspecific binding sites, and incubated the plate with plasma, immobilizing the lipoprotein particles containing both ApoA-II and ApoA-I The unbound constituents of plasma were washed away, peroxidase-labeled antibody to ApoA-I was added, the plate rewashed, peroxidase substrate added, and the resulting color measured ApoA-I unassociated with ApoA-II was evaluated by subtracting the concentration of associated ApoA-I from the total ApoA-I concentration The method is specific, rapid, and precise Within- and between-assay CVs were 56 and 98%, respectively Analytical recovery of ApoA-I was 94% The average normolipidemic concentration of ApoA-I associated with ApoA-II in 50 women was 790 mg/L; in 50 men, it was 788 mg/L The corresponding values for unassociated ApoA-I were 644, 577 mg/L Both lipoprotein forms of ApoA-I were detected in all major density classes, but were most abundant in high-density lipoproteins The technique is applicable to measurement of any two apolipoproteins that occur in both associated and unassociated forms in plasma

Quantification of two different types of apolipoprotein A-I containing lipoprotein particles in plasma by enzyme-linked differential-antibody immunosorbent assay.

A noncompetitive enzyme-linked immunosorbent assay (ELISA) for apolipoprotein A-II (ApoA-II) was developed. Microtiter plates were coated with affinity purified antibodies to ApoA-II. After incubation with human plasma, the amount of ApoA-II bound to the coated plate was determined with peroxidase-labeled antibodies to ApoA-II. When pure ApoA-II or delipidated reference plasma was used as standard, a single step delipidation was required in order to unmask some antigenic sites of ApoA-II. However, the underestimated ApoA-II values in untreated samples were shown to be corrected by using intact reference plasma as secondary standard. The average concentration of ApoA-II in normolipidemic plasma was 0.376 g/l.

Quantitative determination of human plasma apolipoprotein A-II by a non competitive enzyme-linked immunosorbent assay.

Apolipoprotein A-I containing lipoproteins in coronary artery disease

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

A. Kandoussi

Author Tools

Chat about Author

Papers

Quantification of two different types of apolipoprotein A-I containing lipoprotein particles in plasma by enzyme-linked differential-antibody immunosorbent assay.

Quantitative determination of human plasma apolipoprotein A-II by a non competitive enzyme-linked immunosorbent assay.

Apolipoprotein A-I containing lipoproteins in coronary artery disease