The ability of 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.
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 ATP-binding cassette transporter G1-mediated efflux. This review discusses recent findings that connect HDL composition and CEC.
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. Although 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.
aDepartamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Brazil
bDiabetes Institute, Department of Medicine, University of Washington, Seattle, Washington, USA
Correspondence to Dr Tomáš Vaisar, PhD, Diabetes Institute, Department of Medicine, University of Washington, 850 Republican St, Seattle, WA 98109, USA. Tel: +1 206 616 4972; e-mail: email@example.com