HDL superphospholipidation enhances key steps in reverse cholesterol transport Academic Article uri icon

Overview

MeSH Major

  • Cholesterol
  • Lipoproteins, HDL
  • Phosphatidylcholines

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 approximately 120 to approximately 350kDa. Kinetic analysis of FC efflux to the resulting SPLn particles shows that K(m) and V(max) for SPLn HDL are lower and higher respectively than for native HDL. As a consequence, the catalytic efficiency, V(max)/K(m), 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.

publication date

  • April 2010

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2846204

Digital Object Identifier (DOI)

  • 10.1016/j.atherosclerosis.2009.10.002

PubMed ID

  • 19892352

Additional Document Info

start page

  • 430

end page

  • 5

volume

  • 209

number

  • 2