(Press-News.org) High levels of low-density lipoprotein (LDL) cholesterol increases the risk for coronary heart disease. A variant in the human gene encoding the protein sortilin is associated with reduced plasma LDL levels and a decreased risk of heart attack. This variant results in markedly higher sortilin protein expression in liver. Dr. Daniel Rader and colleagues at the University of Pennsylvania in Philadelphia have uncovered a two-pronged mechanism for the change in LDL observed. Using a mouse model system, the Rader team found that increased liver sortilin is responsible for reducing secretion of APOB, a protein that transports LDL to tissue, and also triggers LDL breakdown. Both of these effects were dependent on a cellular process known as lysosomal targeting. Their data provide functional evidence that genetically-increased hepatic sortilin in humans reduces LDL by increasing LDL degradation, thus removing LDL from circulation, as well as decreasing APOB.
###TITLE:
Hepatic sortilin regulates both apolipoprotein B secretion and LDL catabolism
AUTHOR CONTACT:
Daniel J. Rader
University of Pennsylvania Medical Center, Philadelphia, PA, USA
Phone: 215-898-4011; Fax: 215-573-8606; E-mail: rader@mail.med.upenn.edu
Gene variant reduces cholesterol by 2 mechanisms
2012-07-03
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JCI early table of contents for July 2, 2012
2012-07-03
CARDIOVASCULAR DISEASE
Gene variant reduces cholesterol by two mechanisms
High levels of low-density lipoprotein (LDL) cholesterol increases the risk for coronary heart disease. A variant in the human gene encoding the protein sortilin is associated with reduced plasma LDL levels and a decreased risk of heart attack. This variant results in markedly higher sortilin protein expression in liver. Dr. Daniel Rader and colleagues at the University of Pennsylvania in Philadelphia have uncovered a two-pronged mechanism for the change in LDL observed. Using a mouse model system, ...
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