ApoA-IV promotes the biogenesis of apoA-IV-containing HDL particles with the participation of ABCA1 and LCAT

Duka, Adelina; Fotakis, Panagiotis; Georgiadou, Dimitra G.; Kateifides, Andreas; Tzavlaki, Kalliopi; Eckardstein, Leonardo von; Stratikos, Efstratios; Kardassis, Dimitris; Zannis, Vassilis I.

doi:10.1194/jlr.m030114

Cited by 36 publications

(31 citation statements)

References 67 publications

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“…However, because we have shown that SI-HDL is rich in apo AIV, our fi nding is consistent with that of Duka et al ( 56 ), who showed that ABCA1 and LCAT participate in the biogenesis of apo-AIV-containing particles by using ABCA1…”

Section: Discussionsupporting

confidence: 82%

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Selective evaluation of high density lipoprotein from mouse small intestine by an in situ perfusion technique

Yamaguchi

Zhang

Tomonaga

et al. 2014

Journal of Lipid Research

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HDL is unquestionably a major antiatherogenic factor worldwide, regardless of sex, race, and age ( 1, 2 ). Therefore, an increase in HDL levels has been an important goal that guides the development of novel therapies for atherosclerotic cardiovascular diseases ( 3 ) because it was reported that plasma HDL cholesterol (HDL-C) levels were reduced in patients with ischemic heart disease and stroke ( 4, 5 ). Strategies for raising HDL are now available. Because remarkable progress has been made in our understanding of the molecular mechanism of HDL production, enhanced production is one of the major strategies for raising HDL.ABCA1, mutations of which are the genetic cause of Tangier disease and genetic HDL defi ciency, is one of the Abstract The small intestine (SI) is the second-greatest source of HDL in mice. However, the selective evaluation of SI-derived HDL (SI-HDL) has been diffi cult because even the origin of HDL obtained in vivo from the intestinal lymph duct of anesthetized rodents is doubtful. To shed light on this question, we have developed a novel in situ perfusion technique using surgically isolated mouse SI, with which the possible fi ltration of plasma HDL into the SI lymph duct can be prevented. With the developed method, we studied the characteristics of and mechanism for the production and regulation of SI-HDL. Nascent HDL particles were detected in SI lymph perfusates in WT mice, but not in ABCA1 KO mice. SI-HDL had a high protein content and was smaller than plasma HDL. SI-HDL was rich in TG and apo AIV compared with HDL in liver perfusates. SI-HDL was increased by high-fat diets and reduced in apo E KO mice. In conclusion, with our in situ perfusion model that enables the selective evaluation of SI-HDL, we demonstrated that ABCA1 plays an important role in intestinal HDL production, and SI-HDL is small, dense, rich in apo AIV, and regulated by nutritional and genetic factors.

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Section: Discussionsupporting

confidence: 82%

“…C: Comparison of SI-HDL production in 14-week-old WT and apo E KO mice. However, Duka et al ( 56 ) showed that apo-AIV-containing HDL is formed in the absence of apo AI by using apo AI -/ -mice that had been transfected with the apo AIV gene. Therefore, apo AIV coexists with apo AI but can form HDL independent of apo AI if apo AI is absent.…”

Section: Discussionmentioning

confidence: 99%

Selective evaluation of high density lipoprotein from mouse small intestine by an in situ perfusion technique

Yamaguchi

Zhang

Tomonaga

et al. 2014

Journal of Lipid Research

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show abstract

“…Other mutations lead to very low levels of HDL cholesterol and accumulation presence of apoB-48 in the higher density fractions affected the particle composition of the HDL fraction by enriching it with larger particles corresponding in size to VLDL, IDL, and LDL. Previous studies showed that apoA-IV can also generate apoA-IV containing HDL particles ( 21 ). It is thus possible that apoA-IV containing HDL may fuse with apoB-48 containing particles and pull them toward the higher density regions.…”

Section: Lcat Corrects the Aberrant Hdl Phenotype Caused By The Apoa-mentioning

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

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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

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“…We showed recently that apoE-or apoA-IV-containing HDL particles can be formed following a pathway similar to that used for the generation of apoA-I-containing HDL particles ( 28,35 ). Since the HDL fractions 6 and 7 analyzed by EM contained both apoA-I[218-222] mutant and mouse apoE, we considered the possibility that the observed spherical HDL particles in Fig.…”

Section: Rationale For Selection Of the Mutationsmentioning

confidence: 99%

“…4D ). It is possible that the LDL-and IDLsized particles might arise by initial formation of apoA-IVcontaining HDL ( 28 ) and subsequent fusion of such HDL particles with apoB-containing lipoproteins ( Fig. 4C, D ).…”

Section: Comparative Analysis Of the In Vitro Functions Of Wt Apoa-imentioning

confidence: 99%

Role of the hydrophobic and charged residues in the 218–226 region of apoA-I in the biogenesis of HDL

Fotakis

Kateifides

Gkolfinopoulou

et al. 2013

Journal of Lipid Research

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ApoA-IV promotes the biogenesis of apoA-IV-containing HDL particles with the participation of ABCA1 and LCAT

Cited by 36 publications

References 67 publications

Selective evaluation of high density lipoprotein from mouse small intestine by an in situ perfusion technique

Selective evaluation of high density lipoprotein from mouse small intestine by an in situ perfusion technique

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

Role of the hydrophobic and charged residues in the 218–226 region of apoA-I in the biogenesis of HDL

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