Laboratory Assessment of HDL Heterogeneity and Function

Abstract

Background: Plasma concentrations of HDL cholesterol (HDL-C) and its major protein component apolipoprotein (apo) A-I are strongly inversely associated with cardiovascular risk, leading to the concept that therapy to increase HDL-C and apoA-I concentrations would be antiatherosclerotic and protective against cardiovascular events. The recent failure of the drug torcetrapib, a cholesteryl ester transfer protein inhibitor that substantially increased HDL-C concentrations, has brought focus on the issues of HDL heterogeneity and function as distinct from HDL-C concentrations. Content: This review addresses the current state of knowledge regarding assays of HDL heterogeneity and function and their relationship to cardiovascular disease. HDL is highly heterogeneous, with subfractions that can be identified on the basis of density, size, charge, and protein composition, and the concept that certain subfractions of HDL may be better predictors of cardiovascular risk is attractive. In addition, HDL has been shown to have a variety of functions that may contribute to its cardiovascular protective effects, including promotion of macrophage cholesterol efflux and reverse cholesterol transport and antiinflammatory and nitric oxide–promoting effects. Summary: Robust laboratory assays of HDL subfractions and functions and validation of the usefulness of these assays for predicting cardiovascular risk and assessing response to therapeutic interventions are critically important and of great interest to cardiovascular clinicians and investigators and clinical chemists.

Mass spectrometric determination of apolipoprotein molecular stoichiometry in reconstituted high density lipoprotein particles

“…Currently, there is a great deal of research interest focused on developing therapeutic methods to increase HDL-cholesterol and plasma apoA-I levels and to enhance the beneficial functional properties of HDL (3,4). HDL complexes are heterogeneous in density, shape, size, surface charge, type of apolipoproteins present, as well as number of apolipoprotein molecules present per particle (5)(6)(7). HDL consists of ?50% protein by mass where apoA-I and apoA-II comprise 70 and 20% of the protein mass, respectively.…”

The biological activity of high-density lipoprotein fractions and their role in the development of cardiovascular diseases

“…Эти различия по профилям частиц ЛПВП, полученные различными методами, очевидно, связаны с противоречивыми данными о связи фракций ЛПВП с прогнозированием ИБС. Таким образом, уровень ХС, связанный с большим количеством как ЛПВП2, так и ЛПВП3, может рас-сматриваться как негативный прогностически фактор риска раз-вития ССЗ [24]. Для согласования данных по профилям частиц ЛПВП, полученных с использованием различных методологий, недавно предложена новая номенклатура ЛПВП.…”

Polydextrose in Lipid Metabolism

“…HDL is highly heterogeneous, and subfractions of it can be identified on the basis of density, size, charge, and protein composition [56]. Different fractions of HDL can be identified by ultracentrifugation, gradient gel electrophoresis, and nuclear magnetic resonance (NMR) spectroscopy, and these different fractions could play diverse roles in protective function [56,57].…”

“…Different fractions of HDL can be identified by ultracentrifugation, gradient gel electrophoresis, and nuclear magnetic resonance (NMR) spectroscopy, and these different fractions could play diverse roles in protective function [56,57]. It is thought that certain fractions of HDL cholesterol could be better predictors of cardiovascular diseases and its risk.…”