Changing Perspectives on HDL: From Simple Quantity Measurements to Functional Quality Assessment

Abstract

High-density lipoprotein (HDL) comprises a heterogeneous group of particles differing in size, density, and composition. HDL cholesterol (HDL-C) levels have long been suggested to indicate cardiovascular risk, inferred from multiple epidemiological studies. The failure of HDL-C targeted interventions and genetic studies has raised doubts on the atheroprotective role of HDL-C. The current consensus is that HDL-C is neither a biomarker nor a causative agent of cardiovascular disorders. With better understanding of the complex nature of HDL which comprises a large number of proteins and lipids with unique functions, recent focus has shifted from HDL quantity to HDL quality in terms of atheroprotective functions. The current research is focused on developing laboratory assays to assess HDL functions for cardiovascular risk prediction. Also, HDL mimetics designed based on the key determinants of HDL functions are being investigated to modify cardiovascular risk. Improving HDL functions by altering its composition is the key area of future research in HDL biology to reduce cardiovascular risk.

What characterizes event-free elderly FH patients? A comprehensive lipoprotein profiling

“…We can only speculate whether the differences in lipid composition between the two FH groups also reflect functional differences. However, different components of HDL e such as the TG content e contribute to the particle's functionality and potentially anti-atherogenic properties [33]. Indeed, both the HDL particle's lipidome and proteome affect its function, and could perhaps also to some degree be used as a proxy of the function in absence of more comprehensive assays.…”

A Potential Interplay between HDLs and Adiponectin in Promoting Endothelial Dysfunction in Obesity

“…Considering the several functions of HDLs and the numerous changes of their composition induced by LGCI, it is quite evident that the function of HDLs cannot be assessed by considering only their cholesterol levels. The discovery almost 30 years ago that HDLs can be converted from anti-inflammatory particles into proinflammatory particles during an acute response in humans [ 151 ] and a series of subsequent studies (revised in [ 152 ]) have brought out a new perspective on HDLs, namely that structural changes closely related to the functional state of HDLs and the assessment of HDLs function may be more relevant than cholesterol levels to represent HDLs effects on the organism [ 57 , 153 , 154 , 155 , 156 , 157 ]. This led initially to the study of key structural factors such as ApoA-I, MPO and PON-1 as potential markers of the functional capacity of HDLs [ 152 , 158 , 159 , 160 ], and subsequently to a more complete evaluation of the composition of these lipoproteins with omics techniques, such as lipidomic and proteomic [ 161 , 162 ].…”

HDL Is Not Dead Yet

“…The HDL-mediated delivery Biomedicines 2022, 10, 128 2 of 15 of cholesterol from the periphery to the liver for subsequent excretion as free cholesterol or after conversion to bile acids is called the reverse cholesterol transport (RCT) pathway. HDL has been attributed with many different protective effects and pathways in addition to the abovementioned RCT, including cholesterol delivery to steroidogenic organs, anti-inflammatory effects on endothelial cells and macrophages, anti-apoptotic effects on endothelial cells, antithrombotic effects, re-endotheliazation of injured arteries, and anti-oxidant activity [6,7]. Indeed, in hyperlipidemic mouse atherosclerosis studies, overexpression of transgenic human apoA1 led to increases in HDL-C and RCT and decreases in the extent of atherosclerosis [8,9].…”