Mathematical Modelling of Material Transfer to High-Density Lipoprotein (HDL) upon Triglyceride Lipolysis by Lipoprotein Lipase: Relevance to Cardioprotective Role of HDL - Sorbonne Université Access content directly
Journal Articles Metabolites Year : 2022

Mathematical Modelling of Material Transfer to High-Density Lipoprotein (HDL) upon Triglyceride Lipolysis by Lipoprotein Lipase: Relevance to Cardioprotective Role of HDL

Abstract

High-density lipoprotein (HDL) contributes to lipolysis of triglyceride-rich lipoprotein (TGRL) by lipoprotein lipase (LPL) via acquirement of surface lipids, including free cholesterol (FC), released upon lipolysis. According to the reverse remnant-cholesterol transport (RRT) hypothesis recently developed by us, acquirement of FC by HDL is reduced at both low and extremely high HDL concentrations, potentially underlying the U-shaped relationship between HDL-cholesterol and cardiovascular disease. Mechanisms underlying impaired FC transfer however remain indeterminate. We developed a mathematical model of material transfer to HDL upon TGRL lipolysis by LPL. Consistent with experimental observations, mathematical modelling showed that surface components of TGRL, including FC, were accumulated in HDL upon lipolysis. The modelling successfully reproduced major features of cholesterol accumulation in HDL observed experimentally, notably saturation of this process over time and appearance of a maximum as a function of HDL concentration. The calculations suggested that the both phenomena resulted from competitive fluxes of FC through the HDL pool, including primarily those driven by FC concentration gradient between TGRL and HDL on the one hand and mediated by lecithin-cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) on the other hand. These findings provide novel opportunities to revisit our view of HDL in the framework of RRT.
Fichier principal
Vignette du fichier
metabolites-12-00623-v2.pdf (5.23 Mo) Télécharger le fichier
Origin : Publisher files allowed on an open archive

Dates and versions

hal-03898198 , version 1 (14-12-2022)

Identifiers

Cite

Svetlana Schekatolina, Viktoriia Lahovska, Aleksandr Bekshaev, Sergey Kontush, Wilfried Le Goff, et al.. Mathematical Modelling of Material Transfer to High-Density Lipoprotein (HDL) upon Triglyceride Lipolysis by Lipoprotein Lipase: Relevance to Cardioprotective Role of HDL. Metabolites, 2022, 12 (7), ⟨10.3390/metabo12070623⟩. ⟨hal-03898198⟩
4 View
10 Download

Altmetric

Share

Gmail Facebook X LinkedIn More