Inflammation, remodeling, and other factors affecting HDL cholesterol efflux

Abstract

Purpose of review The ability of high density lipoprotein (HDL) to promote cholesterol efflux from macrophages is a predictor of cardiovascular risk independent of HDL cholesterol levels. However, the molecular determinants of HDL cholesterol efflux capacity (CEC) are largely unknown. Recent findings The term HDL defines a heterogeneous population of particles with distinct size, shape, protein and lipid composition. Cholesterol efflux is mediated by multiple pathways that may be differentially modulated by HDL composition. Furthermore, different subpopulations of HDL particles mediate CEC via specific pathways, but the molecular determinants of CEC, either proteins or lipids, are unclear. Inflammation promotes a profound remodeling of HDL and impairs overall HDL CEC while improving ABCG1-mediated efflux. This review discusses recent findings that connect HDL composition and CEC. Summary Data from recent animal and human studies clearly show that multiple factors associate with CEC including individual proteins, lipid composition, as well as specific particle subpopulations. While acute inflammation remodels HDL and impairs CEC, chronic inflammation has more subtle effects. Standardization of assays measuring HDL composition and CEC is a necessary prerequisite for understanding the factors controlling HDL CEC. Unraveling these factors may help the development of new therapeutic interventions improving HDL function.

Effects of the SGLT2 inhibitor dapagliflozin on HDL cholesterol, particle size, and cholesterol efflux capacity in patients with type 2 diabetes: a randomized placebo-controlled trial

“…However, no change occurred in HDL cholesterol levels, HDL particle size, and activity of enzymes that modulate HDL antioxidant properties (PON1 and ARE) and cholesterol metabolism (CETP). Although the determinants of CEC are partially unknown, inflammation, lipid composition, and HDL particle size have been related to CEC in several populations [30]. As dapagliflozin marginally reduced IL-6 and had no effect on lipid profile and HDL subfractions, the observed reduction in CEC has no clear explanation.…”

Dyslipidemia Management in Adults With Diabetes

“…With greater saturation of lipolysis, hypertriglyceridemia can become severe. Reduced HDL levels in diabetes result from compositional changes mediated by CETP-associated neutral lipid exchange; TG-enriched HDL particles are readily catabolized (8). CETP-mediated TG enrichment and increased lipolysis of LDL by hepatic lipase increase the number of atherogenic small dense LDL particles (9,10).…”

Lipoprotein profiling in early multiple sclerosis patients: effect of chronic inflammation?

“…Furthermore, autoantibodies to apoA-1 and HDL-C have been reported in patients with other autoimmune conditions such as systemic lupus erythematosus, rheumatoid arthritis and antiphospholipid syndrome with reported higher cardiovascular risk and may therefore represent another mechanism potentially leading to proinflammatory properties of apoA-1/HDL-C [34]. The currently accepted concept of HDL-C metabolism describes secretion of small HDL-C particles by the liver and intestine followed by maturation, remodeling and size increase in the circulation by uptake and esterification of cellular cholesterol [39][40][41]. However, recent studies doubted this HDL-C size expansion model of metabolism suggesting HDL-C metabolism occurs mainly within its secreted size rather than progressive maturation of growing particles [39,40].…”

“…The currently accepted concept of HDL-C metabolism describes secretion of small HDL-C particles by the liver and intestine followed by maturation, remodeling and size increase in the circulation by uptake and esterification of cellular cholesterol [39][40][41]. However, recent studies doubted this HDL-C size expansion model of metabolism suggesting HDL-C metabolism occurs mainly within its secreted size rather than progressive maturation of growing particles [39,40].…”