Assessing the functional properties of high-density lipoproteins: an emerging concept in cardiovascular research

Although plasma concentrations of high-density lipoprotein (HDL) cholesterol correlate inversely with the incidence of atherosclerotic cardiovascular disease, results from recent epidemiological, genetic and pharmacological intervention studies resulted in a shift of concept. Rather than HDL cholesterol mass levels, the functionality of HDL particles is increasingly regarded as potentially clinically important. This review provides an overview of four key functional properties of HDL, namely cholesterol efflux and reverse cholesterol transport; antioxidative activities; anti-inflammatory activities; and the ability of HDL to increase vascular nitric oxide production resulting in vasorelaxation. Currently available assays are put into context with different HDL isolation procedures yielding compositional heterogeneity of the particle. Gathered knowledge on the impact of different disease states on HDL function is discussed together with potential underlying causative factors modulating HDL functionalities. In addition, a perspective is provided regarding how a better understanding of the determinants of (dys)functional HDL might impact clinical practice and the future design of rational and specific therapeutic approaches targeting atherosclerotic cardiovascular disease.