ApoA‐I Functions and Synthesis of HDL: Insights from Mouse Models of Human HDL Metabolism

Zannis, Vassilis I.; Zanni, Eleni E.; Papapanagiotou, Angeliki; Kardassis, Dimitris; Fielding, Christopher J.; Chroni, Angeliki

doi:10.1002/9783527625178.ch11

Cited by 4 publications

(7 citation statements)

References 179 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…35,36 Fenofibrate upregulated 5.86-fold, the gene Pltp, and caused a moderate 1.51-fold downregulation of Srb1, two genes that are involved in the remodeling of HDL ( Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…45 Important steps for the maturation of HDL are the esterification of HDL of the nascent particles by Lcat, the transfer of lipids by Pltp, the cholesteryl ester transfer protein and the interaction of the HDL with the HDL receptor (SR-BI) and the ABCG1 lipid transporter. 28,35,45 The fenofibrate treatment significantly downregulated (9.75-fold) the expression of Apoa4 gene. A 10-fold decrease in the Apoa4 gene expression was previously observed in the rat liver by clofibrate treatment.…”

Section: Discussionmentioning

confidence: 98%

See 1 more Smart Citation

Role of Esrrg in the fibrate-mediated regulation of lipid metabolism genes in human ApoA-I transgenic mice

et al. 2009

View full text Add to dashboard Cite

We have used a new ApoA-I transgenic mouse model to identify by global gene expression profiling, candidate genes that affect lipid and lipoprotein metabolism in response to fenofibrate treatment. Multilevel bioinformatical analysis and stringent selection criteria (2-fold change, 0% false discovery rate) identified 267 significantly changed genes involved in several molecular pathways. The fenofibrate-treated group did not have significantly altered levels of hepatic human APOA-I mRNA and plasma ApoA-I compared with the control group. However, the treatment increased cholesterol levels to 1.95-fold mainly due to the increase in high-density lipoprotein (HDL) cholesterol. The observed changes in HDL are associated with the upregulation of genes involved in phospholipid biosynthesis and lipid hydrolysis, as well as phospholipid transfer protein. Significant upregulation was observed in genes involved in fatty acid transport and b-oxidation, but not in those of fatty acid and cholesterol biosynthesis, Krebs cycle and gluconeogenesis. Fenofibrate changed significantly the expression of seven transcription factors. The estrogen receptor-related gamma gene was upregulated 2.36-fold and had a significant positive correlation with genes of lipid and lipoprotein metabolism and mitochondrial functions, indicating an important role of this orphan receptor in mediating the fenofibrate-induced activation of a specific subset of its target genes.

show abstract

“…35,36 Fenofibrate upregulated 5.86-fold, the gene Pltp, and caused a moderate 1.51-fold downregulation of Srb1, two genes that are involved in the remodeling of HDL ( Table 1).…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 98%

Role of Esrrg in the fibrate-mediated regulation of lipid metabolism genes in human ApoA-I transgenic mice

et al. 2009

View full text Add to dashboard Cite

show abstract

“…In previous studies, systematic mutagenesis and gene transfer of human apoA-I mutants in apoA-I-defi cient mice disrupted specifi c steps along the pathway of the biogenesis of HDL and generated discrete HDL phenotypes ( 16 ). These phenotypes were characterized by low HDL levels, preponderance of immature HDL subpopulations, or accumulation of discoidal HDL particles in plasma ( 1,10,11,15,18,19 ).…”

Section: -230 Mutations Are Associated With Abnormalities In the Bmentioning

confidence: 99%

Significance of the hydrophobic residues 225–230 of apoA-I for the biogenesis of HDL

Fotakis

Tiniakou

Kateifides

et al. 2013

Journal of Lipid Research

Self Cite

View full text Add to dashboard Cite

and the biogenesis of HDL but did not identify the apoA-I residues involved ( 1, 2 ). Other studies also showed the importance of the C-terminal region for the structure of apoA-I ( 3-5 ) as well as for other functions of apoA-I ( 6, 7 ). In the preceding article, we investigated the role of the hydrophobic residues L218, L219, V221, and L222 and the charged residues E223 and K226 on the structure and functions of apoA-I and their contribution to the biogenesis of HDL ( 8 ). These studies showed that substitution of the hydrophobic residues L218, L219, V221, and L222 of apoA-I by alanines inhibits the biogenesis and maturation of HDL and generates a phenotype that cannot be corrected by LCAT. Expression of E223 and K226 caused fewer but discrete alterations in the HDL phenotype.The rationale for the present study was that the 225-230 region of apoA-I contains four additional hydrophobic residues that may be equally signifi cant for its structure and functions. For this reason, we used gene transfer in two mouse models as well as biochemical and biophysical analyses to study the impact of substitutions of residues F225, V227, F229, and L230 by alanines on the structure and functions of apoA-I and their impact on the biogenesis of HDL. In vitro experiments showed that the apoA-I[225-230] mutations affected the structure of apoA-I, diminished its capacity to promote ABCA1-mediated cholesterol effl ux, and decreased moderately its ability to activate LCAT. Gene transfer of the apoA-I mutant in apoA-I Previous studies by us showed the overall importance of the 220-231 region of apoA-I for apoA-I/ABCA1 interactions

show abstract

“…The figure is modified from ref. (Zannis et al, 2004b;Zannis et al, 2006b). amino acid repeats which are organized in amphipathic a-helices (Nolte and Atkinson, 1992).…”

Section: Biogenesis Of Hdlmentioning

confidence: 99%

“…High density lipoprotein (HDL) is a macromolecular complex of proteins and lipids that is produced primarily by the liver through a complex pathway that requires initially the functions of apolipoprotein A-I (apoA-I), ATP binding cassette transporter A1 (ABCA1) and lecithin:cholesterol acetyl transferase (LCAT) (Zannis et al, 2006b). Following synthesis, HDL affects the functions of the arterial wall cells through signaling mechanisms mediated by scavenger receptor class B type-I (SR-BI) and other cell surface proteins.…”

Section: Introductionmentioning

confidence: 99%

Pleiotropic Functions of HDL Lead to Protection from Atherosclerosis and Other Diseases

Zannis¹,

Kateifides²,

Fotakis³

et al. 2012

Dyslipidemia - From Prevention to Treatment

Self Cite

View full text Add to dashboard Cite

ApoA‐I Functions and Synthesis of HDL: Insights from Mouse Models of Human HDL Metabolism

Cited by 4 publications

References 179 publications

Role of Esrrg in the fibrate-mediated regulation of lipid metabolism genes in human ApoA-I transgenic mice

Role of Esrrg in the fibrate-mediated regulation of lipid metabolism genes in human ApoA-I transgenic mice

Significance of the hydrophobic residues 225–230 of apoA-I for the biogenesis of HDL

Pleiotropic Functions of HDL Lead to Protection from Atherosclerosis and Other Diseases

Contact Info

Product

Resources

About