One proposal for boosting reverse cholesterol transport has been to elevate plasma HDL levels by inhibiting a protein called CETP that transfers cholesterol esters from HDL to lower-density lipoproteins. However, there has been controversy in the medical literature as to whether CETP deficiency is pro- or anti-atherogenic. Matsuura and colleagues assessed the ability of HDL-2 from individuals deficient in CETP to promote cholesterol removal from macrophages. They observed a 2–3-fold increase in cholesterol efflux in these individuals compared to controls and they demonstrated that this was dependent on a molecule known as ABCG1, which is present on macrophages and contributes to the formation of HDL. They also found that the enhanced ability to promote cholesterol removal in these CETP-deficient individuals was due to increased amounts of the enzyme LCAT and apolipoprotein E in HDL-2, which allow the inner cholesterol ester–rich core of HDL-2 to expand to carry greater amounts of cholesterol. In an accompanying commentary, Robert Mahley and colleagues from the University of California, San Francisco, comment that as CETP does not appear to be essential for reverse cholesterol transport in humans, this raises the hope of using a CETP inhibitor to elevate HDL levels and therefore reduce the incidence of atherosclerosis.
TITLE: HDL from CETP-deficient subjects shows enhanced ability to promote cholesterol efflux from macrophages in an apoE- and ABCG1-dependent pathway
AUTHOR CONTACT:
Fumihiko Matsuura
Osaka University, Osaka, Japan.
Phone: 81-6-6879-3732; Fax: 81-6-6879-3739; E-mail: fc-mastu@fb4.so-net.ne.jp
View the PDF of this article at: https://www.the-jci.org/article.php?id=27602
ACCOMPANYING COMMENTARY
TITLE: Putting cholesterol in its place: apoE and reverse cholesterol transport
AUTHOR CONTACT:
Robert W. Mahley
Gladstone Institute of Neurological Disease, San Francisco, California, USA.
Phone: (415) 734-2000; Fax: (415) 355-0820; E-mail: rmahley@gladstone.ucsf.edu
View the PDF of this article at: https://www.the-jci.org/article.php?id=28632
Journal of Clinical Investigation