High-Density Lipoprotein in Metabolic Disorders and Beyond: An Exciting NewWorld Full of Challenges and Opportunities
Metadata
Show full item recordEditorial
MDPI
Materia
High-density lipoprotein Atherosclerosis NAFLD Type 2 diabetes mellitus Morbid obesity Adipose tissue Multiple myeloma Gene editing Pharmacology Pharmaceutical
Date
2023-06-08Referencia bibliográfica
Zvintzou, E.; Xepapadaki, E.; Skroubis, G.; Mparnia, V.; Giannatou, K.; Benabdellah, K.; Kypreos, K.E. High-Density Lipoprotein in Metabolic Disorders and Beyond: An Exciting NewWorld Full of Challenges and Opportunities. Pharmaceuticals 2023, 16, 855. [https:// doi.org/10.3390/ph16060855]
Abstract
High-density lipoprotein (HDL) is an enigmatic member of the plasma lipid and lipoprotein
transport system, best known for its ability to promote the reverse cholesterol efflux and the
unloading of excess cholesterol from peripheral tissues. More recently, data in experimental mice
and humans suggest that HDL may play important novel roles in other physiological processes
associated with various metabolic disorders. Important parameters in the HDL functions are its
apolipoprotein and lipid content, further reinforcing the principle that HDL structure defines its
functionality. Thus, based on current evidence, low levels of HDL-cholesterol (HDL-C) or dysfunctional
HDL particles contribute to the development of metabolic diseases such as morbid obesity,
type 2 diabetes mellitus, and nonalcoholic fatty liver disease. Interestingly, low levels of HDL-C
and dysfunctional HDL particles are observed in patients with multiple myeloma and other types of
cancer. Therefore, adjusting HDL-C levels within the optimal range and improving HDL particle
functionality is expected to benefit such pathological conditions. The failure of previous clinical
trials testing various HDL-C-raising pharmaceuticals does not preclude a significant role for HDL
in the treatment of atherosclerosis and related metabolic disorders. Those trials were designed on
the principle of “the more the better”, ignoring the U-shape relationship between HDL-C levels
and morbidity and mortality. Thus, many of these pharmaceuticals should be retested in appropriately
designed clinical trials. Novel gene-editing-based pharmaceuticals aiming at altering the
apolipoprotein composition of HDL are expected to revolutionize the treatment strategies, improving
the functionality of dysfunctional HDL.