What does procollagen C-endopeptidase enhancer protein 2 have to do with HDL-cholesteryl ester uptake? Or how I learned to stop worrying and love reverse cholesterol transport? Curr Opin Lipidol 2015 Oct;26(5):420-5
Date
07/29/2015Pubmed ID
26218419Pubmed Central ID
PMC4564020DOI
10.1097/MOL.0000000000000211Scopus ID
2-s2.0-84944345774 (requires institutional sign-in at Scopus site) 12 CitationsAbstract
PURPOSE OF REVIEW: The purpose of this study is to provide an update on the role HDL apolipoprotein A-I plays in reducing the risk of cardiovascular disease (CVD) and how it relates to reverse cholesterol transport (RCT).
RECENT FINDINGS: Despite numerous studies showing that plasma HDL cholesterol concentrations are correlated with a reduced risk of CVD, pharmacologic elevation of HDL has not shown any beneficial effects to date. In contrast, studies correlating the measure of an individual's plasma cholesterol efflux capacity show greater promise as a tool for assessing CVD risk. Although ATP-binding cassette transporter 1-mediated lipidation of apoA-I is considered the principal source of plasma HDL, it represents only one side of the RCT pathway. Equally important is the second half of the RCT pathway in which the liver scavenger receptor class B1 selectively removes HDL cholesteryl esters for excretion. The combined action of the two enzyme systems is reflected in the overall steady-state concentration of plasma HDL cholesterol. For example, reduced ATP-binding cassette transporter 1-mediated production of nascent HDL lowers plasma HDL concentration, just as an increase in cholesteryl ester uptake by scavenger receptor class B1 reduces HDL levels. Thus, the complexity of intravascular HDL metabolism suggests that steady-state plasma HDL concentrations do not provide adequate information regarding an individual's HDL quality or function. Herein, we describe a new player, procollagen C-endopeptidase enhancer 2, which shows atheroprotective function and influences both sides of RCT by enhancing production and catabolism of HDL cholesteryl esters.
SUMMARY: The discovery of a new molecule, procollagen C-endopeptidase enhancer 2, implicated in the regulation of HDL cholesteryl ester concentrations suggests that the extracellular matrix and the proteins that regulate its function represent a new and as yet unexplored realm of HDL cholesterol metabolism.
Author List
Sorci-Thomas MG, Pollard RD, Thomas MJAuthor
Mary Sorci Thomas PhD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAtherosclerosis
Biological Transport
Cholesterol Esters
Extracellular Matrix Proteins
Glycoproteins
Humans
Lipoproteins, HDL
