TY - JOUR

T1 - Protein-based HDL subspecies

T2 - Rationale and association with cardiovascular disease, diabetes, stroke, and dementia

AU - Sacks, F. M.

AU - Furtado, J. D.

AU - Jensen, M. K.

PY - 2022

Y1 - 2022

N2 - HDL-cholesterol is associated with reduced risk of cardiovascular disease, and is used in clinical practice for risk stratification. HDL is composed of many protein-defined subspecies that each comprises just a few percent of the total, some associated with lower and some with higher risk of CVD. HDL that contains apoC3 or apoE are subspecies that have opposing actions on HDL reverse cholesterol transport and opposing associations with risk of future CVD, apoC3 adverse and apoE beneficial. In addition to coronary heart disease, HDL that contains apoC3 is associated with risk of future type 2 diabetes and insulin resistance; ischemic stroke and cerebral infarction; dementia and the deposition of beta-amyloid in the brain. HDL that contains apoE and apoE itself are associated with lower risk of dementia. Other HDL subspecies that contain complement C3, alpha-2 macroglobulin, plasminogen, or haptoglobin are associated with higher future risk of coronary heart disease, whereas others such as HDL that contains apoC1 are associated with lower risk. At this time, these findings provide improved understanding of the multifaceted HDL system to better determine risk and targeting of therapy for the most prevalent chronic lifestyle diseases in our society.

AB - HDL-cholesterol is associated with reduced risk of cardiovascular disease, and is used in clinical practice for risk stratification. HDL is composed of many protein-defined subspecies that each comprises just a few percent of the total, some associated with lower and some with higher risk of CVD. HDL that contains apoC3 or apoE are subspecies that have opposing actions on HDL reverse cholesterol transport and opposing associations with risk of future CVD, apoC3 adverse and apoE beneficial. In addition to coronary heart disease, HDL that contains apoC3 is associated with risk of future type 2 diabetes and insulin resistance; ischemic stroke and cerebral infarction; dementia and the deposition of beta-amyloid in the brain. HDL that contains apoE and apoE itself are associated with lower risk of dementia. Other HDL subspecies that contain complement C3, alpha-2 macroglobulin, plasminogen, or haptoglobin are associated with higher future risk of coronary heart disease, whereas others such as HDL that contains apoC1 are associated with lower risk. At this time, these findings provide improved understanding of the multifaceted HDL system to better determine risk and targeting of therapy for the most prevalent chronic lifestyle diseases in our society.

KW - HDL

KW - Proteomics

KW - Apolipoproteins C3 and E

KW - Cardiovascular disease

KW - Diabetes

KW - Dementia

KW - HIGH-DENSITY-LIPOPROTEIN

KW - CORONARY-ARTERY-DISEASE

KW - ESTER TRANSFER PROTEIN

KW - APOLIPOPROTEIN C-III

KW - PLASMA-LIPOPROTEINS

KW - ALZHEIMERS-DISEASE

KW - CHOLESTEROL EFFLUX

KW - PROTEOMIC ANALYSIS

KW - RISK

KW - BETA

U2 - 10.1016/j.bbalip.2022.159182

DO - 10.1016/j.bbalip.2022.159182

M3 - Journal article

C2 - 35605828

VL - 1867

JO - B B A - Molecular and Cell Biology of Lipids

JF - B B A - Molecular and Cell Biology of Lipids

SN - 1388-1981

IS - 9

M1 - 159182

ER -