TY - JOUR
T1 - JCL roundtable
T2 - High-density lipoprotein function and reverse cholesterol transport
AU - Cuchel, Marina
AU - Rohatgi, Anand
AU - Sacks, Frank M.
AU - Guyton, John R.
N1 - Funding Information:
Authors have received funding from commercial sources as indicated under Disclosures and from noncommercial sources as follows: Dr. Guyton, Harry and Beatrice Sley Foundation; Dr. Cuchel, National Institutes of Health HL059407; Dr. Rohatgi, National Institutes of Health K08HL118131, R01HL136724, R21HL137450 and American Heart Association 17UNPG33840006; and Dr. Sacks, National Institutes of Health R01HL095964.
Publisher Copyright:
© 2018 National Lipid Association
PY - 2018/9/1
Y1 - 2018/9/1
N2 - High-density lipoproteins (HDL) have been known since the 1960s to be associated with protection from atherosclerotic cardiovascular disease. However, the mechanisms of this protection are unclear. The extent to which HDL per se vs other correlated metabolic factors may mitigate atherosclerosis has been seriously questioned. In fact, new epidemiologic studies have found that in some clinical settings, very high HDL cholesterol levels correlate with increased atherosclerotic risk. Most importantly, over the past 2 decades, randomized clinical trials targeting HDL have failed to reproduce the usual epidemiologic inverse relation of HDL cholesterol to atherosclerotic events. In this roundtable discussion, we bring together 3 expert investigators working in the HDL field to elucidate questions of HDL function. One area of agreement is that reverse cholesterol transport remains a primary hypothesis for an anti-atherogenic role of HDL. Bioassays that measure cholesterol efflux capacity of HDL (or of apolipoprotein [apo] B-depleted plasma) have emerged as potentially accurate surrogates for reverse cholesterol transport. ApoA-I is the major functional apoprotein of HDL, but apoE- and apoC-III-containing subpopulations of HDL may have significant roles. Anti- and pro-inflammatory functions of various HDL particles, as well as the role of oxidative and other modifications, are gaining attention.
AB - High-density lipoproteins (HDL) have been known since the 1960s to be associated with protection from atherosclerotic cardiovascular disease. However, the mechanisms of this protection are unclear. The extent to which HDL per se vs other correlated metabolic factors may mitigate atherosclerosis has been seriously questioned. In fact, new epidemiologic studies have found that in some clinical settings, very high HDL cholesterol levels correlate with increased atherosclerotic risk. Most importantly, over the past 2 decades, randomized clinical trials targeting HDL have failed to reproduce the usual epidemiologic inverse relation of HDL cholesterol to atherosclerotic events. In this roundtable discussion, we bring together 3 expert investigators working in the HDL field to elucidate questions of HDL function. One area of agreement is that reverse cholesterol transport remains a primary hypothesis for an anti-atherogenic role of HDL. Bioassays that measure cholesterol efflux capacity of HDL (or of apolipoprotein [apo] B-depleted plasma) have emerged as potentially accurate surrogates for reverse cholesterol transport. ApoA-I is the major functional apoprotein of HDL, but apoE- and apoC-III-containing subpopulations of HDL may have significant roles. Anti- and pro-inflammatory functions of various HDL particles, as well as the role of oxidative and other modifications, are gaining attention.
KW - Apolipoprotein A-I
KW - Apolipoprotein C-III
KW - Apolipoprotein E
KW - Cholesterol efflux capacity
KW - High-density lipoproteins
KW - Reverse cholesterol transport
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U2 - 10.1016/j.jacl.2018.09.005
DO - 10.1016/j.jacl.2018.09.005
M3 - Review article
C2 - 30314802
AN - SCOPUS:85054459364
SN - 1933-2874
VL - 12
SP - 1086
EP - 1094
JO - Journal of Clinical Lipidology
JF - Journal of Clinical Lipidology
IS - 5
ER -