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HDL superphospholipidation enhances key steps in reverse cholesterol transport

  • Urbain Tchoua
    Affiliations
    Section of Atherosclerosis and Vascular Medicine, Department of Medicine, Baylor College of Medicine, MS A-601, 6565 Fannin Street, Houston, TX 77030, USA
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  • Baiba K. Gillard
    Affiliations
    Section of Atherosclerosis and Vascular Medicine, Department of Medicine, Baylor College of Medicine, MS A-601, 6565 Fannin Street, Houston, TX 77030, USA
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  • Henry J. Pownall
    Correspondence
    Corresponding author. Tel.: +1 713 798 4160; fax: +1 713 798 9005.
    Affiliations
    Section of Atherosclerosis and Vascular Medicine, Department of Medicine, Baylor College of Medicine, MS A-601, 6565 Fannin Street, Houston, TX 77030, USA
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      Abstract

      HDL-phospholipids (HDL-PL) play an important role in reverse cholesterol transport (RCT). Phosphatidylcholine (PC) is the most important phospholipid in RCT because it is the essential cholesterol-binding component of lipoproteins and is the acyl donor in the esterification of FC by lecithin:cholesterol acyltransferase (LCAT). FC efflux to sera is a positive anti-atherogenic function of HDL-PL. Although PC has long been recognized as an anti-atherogenic agent, development of new HDL therapies based on PC has been fraught with issues of efficacy, cost, and safety. Moreover, some methods to increase HDL-PC perturb HDL and release lipid-free apolipoproteins (apo) A-I. We developed a new method, HDL SPLn (SPLn) using a modified detergent removal method that obviates these concerns. SPLn can incorporate PC into HDL and increase HDL-PC > 10-fold. This is achieved with no loss of apo A-I. According to size exclusion chromatography and native gradient gel electrophoresis, SPLn raises the HDL particle weight in a dose-dependent way, from ∼120 to ∼350 kDa. Kinetic analysis of FC efflux to the resulting SPLn particles shows that Km and Vmax for SPLn HDL are lower and higher respectively than for native HDL. As a consequence, the catalytic efficiency, Vmax/Km, increases by more than 400%. Clinically, small increases in serum HDL-PL are associated with significant and profound increases in FC efflux to serum. Treatment of relatively small amounts of plasma by SPLn is a potential method of improving at least one step in RCT.

      Abbreviations:

      Apo (apolipoprotein), DP (detergent perturbation), HDL (high density lipoproteins), FC (free cholesterol), CE (cholesteryl ester), POPC (1-palmitoyl-2-oleoyl phosphatidylcholine), LCAT (lecithin:cholesterol acyltransferase), RCT (reverse cholesterol transport), SEC (size exclusion chromatography), SPLd (superphospholipidated), SPLn (superphospholipidation), TBS (Tris-buffered saline), ABC (ATP-binding cassette transporter), SR-BI (scavenger receptor, classB, typeI)

      Keywords

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