HDL superphospholipidation enhances key steps in reverse cholesterol transport

Research output: Contribution to journalArticle

26 Scopus citations

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 ∼350kDa. 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.

Original languageEnglish (US)
Pages (from-to)430-435
Number of pages6
JournalAtherosclerosis
Volume209
Issue number2
DOIs
StatePublished - Apr 2010

Keywords

  • Cholesterol transport
  • HDL therapy
  • Lipid transport
  • Lipoproteins
  • SR-BI

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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