Journal
CIRCULATION RESEARCH
Volume 124, Issue 10, Pages 1505-1518Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCRESAHA.119.312617
Keywords
atherosclerosis; cardiovascular diseases; cholesterol; diabetes mellitus; foam cells; reverse cholesterol transport
Funding
- Canadian Institutes for Health Research [PJT-391187]
- Heart and Stroke Foundation of Canada
- American Heart Association [18CDA34110203AHA]
- National Institutes of Health [DK095684, HL084312, HL129433, HL092969, HL122728, HL117226, HL131481]
- Department of Defense [W81XWH-15-1-0374, W81XWH-16-1-0255]
- Canada Research Chair
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Cardiovascular disease, with atherosclerosis as the major underlying factor, remains the leading cause of death worldwide. It is well established that cholesterol ester-enriched foam cells are the hallmark of atherosclerotic plaques. Multiple lines of evidence support that enhancing foam cell cholesterol efflux by HDL (high-density lipoprotein) particles, the first step of reverse cholesterol transport (RCT), is a promising antiatherogenic strategy. Yet, excitement towards the therapeutic potential of manipulating RCT for the treatment of cardiovascular disease has faded because of the lack of the association between cardiovascular disease risk and what was typically measured in intervention trials, namely HDL cholesterol, which has an inconsistent relationship to HDL function and RCT. In this review, we will summarize some of the potential reasons for this inconsistency, update the mechanisms of RCT, and highlight conditions in which impaired HDL function or RCT contributes to vascular disease. On balance, the evidence still argues for further research to better understand how HDL functionality contributes to RCT to develop prevention and treatment strategies to reduce the risk of cardiovascular disease.
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