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. 2017 Nov 4;31(6):471-485.
doi: 10.7555/JBR.31.20160082. Online ahead of print.

Role of apolipoproteins, ABCA1 and LCAT in the biogenesis of normal and aberrant high density lipoproteins

Vassilis I Zannis  1 , Shi Su  2 , Panagiotis Fotakis  1
Affiliations

Role of apolipoproteins, ABCA1 and LCAT in the biogenesis of normal and aberrant high density lipoproteins

Vassilis I Zannis et al. J Biomed Res. .

Abstract

In this review, we focus on the pathway of biogenesis of HDL, the essential role of apoA-I, ATP binding cassette transporter A1 (ABCA1), and lecithin: cholesterol acyltransferase (LCAT) in the formation of plasma HDL; the generation of aberrant forms of HDL containing mutant apoA-I forms and the role of apoA-IV and apoE in the formation of distinct HDL subpopulations. The biogenesis of HDL requires functional interactions of the ABCA1 with apoA-I (and to a lesser extent with apoE and apoA-IV) and subsequent interactions of the nascent HDL species thus formed with LCAT. Mutations in apoA-I, ABCA1 and LCAT either prevent or impair the formation of HDL and may also affect the functionality of the HDL species formed. Emphasis is placed on three categories of apoA-I mutations. The first category describes a unique bio-engineered apoA-I mutation that disrupts interactions between apoA-I and ABCA1 and generates aberrant preβ HDL subpopulations that cannot be converted efficiently to α subpopulations by LCAT. The second category describes natural and bio-engineered apoA-I mutations that generate preβ and small size α4 HDL subpopulations, and are associated with low plasma HDL levels. These phenotypes can be corrected by excess LCAT. The third category describes bio-engineered apoA-I mutations that induce hypertriglyceridemia that can be corrected by excess lipoprotein lipase and also have defective maturation of HDL. The HDL phenotypes described here may serve in the future for diagnosis, prognoses and potential treatment of abnormalities that affect the biogenesis and functionality of HDL.

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Figures

Fig.1
Fig.1
The pathway of the biogenesis of HDL and the consequence of mutations in apoA-I, ABCA1 and LCAT.
Fig.2
Fig.2
Analyses of the phenotype of the apoA-I[218-222] mutation that inhibits the conversion of the preβ to αHDL particles and the apoA-I[L141R]Pisa mutation that influences the activity of LCAT and is associated with low plasma HDL levels.
Fig.3
Fig.3
Analyses of the phenotype of the apoA-I[D89A/E91A/E92A] mutation that induces hypertriglyceridemia and the potential role of solvent inaccessible salt bridges in the induction of hypertriglyceridemia.
Fig.4
Fig.4
Schematic representation of the secondary structure of apoA-I[,–82].
Fig.5
Fig.5
Participation of apoE and apoA-IV in the biogenesis of apoE- and apoA-IV containing HDL particles.
See this image and copyright information in PMC

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