on September 14, 2006
Published online before print September 14, 2006, doi: 10.1161/01.ATV.0000245791.53245.ee
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on July 10, 2006
Accepted on August 30, 2006
NPC1L1: Evolution From Pharmacological Target to Physiological Sterol Transporter
Murray W. Huff ;
From Vascular Biology Group, Robarts Research Institute, London, Ontario, Canada.
* To whom correspondence should be addressed. E-mail: hegele{at}robarts.ca.
Abstract--Niemann-Pick C1-like 1 protein (NPC1L1) was recently shown to be the molecular target of the cholesterol absorption inhibitor class of drugs, of which ezetimibe is the first widely used member. Since its discovery, NPC1L1 has also been shown to play a focal physiological role in intestinal absorption of sterols, including plant sterols and cholesterol. Evidence in support of this new metabolic pathway has been garnered not only through human, animal, and cell studies of function but also through the use of human genetics as an approach to study the association of NPC1L1 sequence variation with metabolic and drug-response phenotypes. The example of NPC1L1 shows how the elucidation of a pharmacological target can serve as a means to gain understanding of a key physiological pathway.
Key words: cholesterol • enterocyte • intestine • lipoproteins • low-density lipoprotein • pharmacogenetics • sterol
This article has been cited by other articles:
 |
|
 |
|
  J Armitage Commentary on NICE technology appraisal guidance on ezetimibe for the treatment of primary (heterozygous-familial and non-familial) hypercholesterolaemia Heart, May 1, 2008; 94(5): 643 - 645. [Full Text] [PDF]
|
|
|
|
 |
|
 A. B. Weinglass, M. G. Kohler, E. O. Nketiah, J. Liu, W. Schmalhofer, A. Thomas, B. Williams, L. Beers, L. Smith, M. Hafey, et al. Madin-Darby Canine Kidney II Cells: A Pharmacologically Validated System for NPC1L1-Mediated Cholesterol Uptake Mol. Pharmacol., April 1, 2008; 73(4): 1072 - 1084. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Charlton-Menys and P. N. Durrington Human cholesterol metabolism and therapeutic molecules Exp Physiol, January 1, 2008; 93(1): 27 - 42. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Hegele and R. L. Pollex Apolipoprotein A-V Genetic Variation and Plasma Lipoprotein Response to Fibrates Arterioscler. Thromb. Vasc. Biol., June 1, 2007; 27(6): 1224 - 1227. [Full Text] [PDF]
|
|
|
|
|
|
H. R. Davis Jr, L. M. Hoos, G. Tetzloff, M. Maguire, L.-j. Zhu, M. P. Graziano, and S. W. Altmann Deficiency of Niemann-Pick C1 Like 1 Prevents Atherosclerosis in ApoE-/- Mice Arterioscler. Thromb. Vasc. Biol., April 1, 2007; 27(4): 841 - 849. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Telford, B. G. Sutherland, J. Y. Edwards, J. D. Andrews, P. H. R. Barrett, and M. W. Huff The molecular mechanisms underlying the reduction of LDL apoB-100 by ezetimibe plus simvastatin J. Lipid Res., March 1, 2007; 48(3): 699 - 708. [Abstract] [Full Text] [PDF]
|
|