Title:High-density Lipoprotein (HDL) Dysfunction and the Future of HDL
Volume: 16
Issue: 5
Author(s): Sibel Ertek*
Affiliation:
- Endocrinology and Metabolic Diseases Department, Memorial Ankara Hospital, Ankara,Turkey
Keywords:
High-density lipoprotein, cholesterol, atherosclerosis, apolipoprotein A-1, dyslipidemia, inflammation,
cardiovascular disease.
Abstract: Although High Density Lipoprotein Cholesterol (HDL-C) levels are inversely proportional to
cardiovascular risk in many studies, recent pharmacological interventional studies with HDL-C raising
strategies did not show a benefit in terms of vascular events. The HDL particle is heterogenous with
anti-atherogenic functions and non-vascular effects. Many factors affect HDL components and may
either cause compositional changes, post-translational modifications of proteins, or alter lipids and other
cargo molecules; generally these factors cause more than one of these changes, resulting in functional
differences. Therefore, the role of lipoproteins change in different physical and disease conditions.
Mainly, in proteome, Apolipoprotein A1 (Apo-A1), Myeloperoxidase (MPO), Paroxonase (PON) are
affected by inflammation or glycation-related factors; and especially esterification or unesterification of
lipids, changes in phospholipid or unsaturated lipid content change the HDL function. Measuring the
HDL-C level is probably not a good predictor of its cardiovascular benefits, and methods to evaluate
HDL functions are required. In current medical practice, it is not simple and feasible to measure
different functions of this lipoprotein, but near-future strategies may be developed. Meanwhile, as we
learn more about HDL structure and the role of each component, we can develop therapeutic approaches
to improve HDL function. Apo-A1-mimetics, reconstituted HDL, nanoparticles and microRNA
therapies could be promising as anti-atherosclerotic therapies. They may even provide useful therapies
for the treatment of some non-cardiovascular diseases.
