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Vassilis I. Zannis,Shi Su,Panagiotis Fotakis.Journal of Biomedical Research,2017,31(6):471-485
Role of apolipoproteins, ABCA1 and LCAT in the biogenesis ofnormal and aberrant high density lipoproteins
Received:July 07, 2016  Revised:July 27, 2016
DOI10.7555/JBR.31.20160082
KeywordsHDL biogenesis, HDL phenotypes, apolipoprotein A-I mutations, apolipoprotein E, apolipoprotein A-IV, ATP- binding cassette transporter A1 (ABCA1)
Grant ProgramThis work was supported by National Institute of Health Grant HL-48739 and HL-68216
AuthorInstitution
Vassilis I. Zannis Molecular Genetics, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA 02118, USA;Department University of Crete, School of Medicine, Heraklion, Crete, Greece
Shi Su Molecular Genetics, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA 02118, USA
Panagiotis Fotakis Molecular Genetics, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA 02118, USA;Department University of Crete, School of Medicine, Heraklion, Crete, Greece
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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 pre HDL subpopulations that cannot be converted efficiently to subpopulations by LCAT. The second category describes natural and bio-engineered apoA-I mutations that generate pre and small size 4 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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