Free cholesterol transfer to high-density lipoprotein (HDL) upon triglyceride lipolysis underlies the U-shape relationship between HDL-cholesterol and cardiovascular disease - Sorbonne Université Access content directly
Journal Articles European Journal of Preventive Cardiology Year : 2020

Free cholesterol transfer to high-density lipoprotein (HDL) upon triglyceride lipolysis underlies the U-shape relationship between HDL-cholesterol and cardiovascular disease

Ma Feng
  • Function : Author
Maryam Darabi
  • Function : Author
Emilie Tubeuf
  • Function : Author
Aurélie Canicio
  • Function : Author
Marie Lhomme
  • Function : Author
Eric Frisdal
  • Function : Author
Sandrine Lanfranchi-Lebreton
  • Function : Author
Lucrèce Matheron
  • Function : Author
Fabiana Rached
  • Function : Author
Maharajah Ponnaiah
  • Function : Author
Carlos Serrano
  • Function : Author
Raul Santos
  • Function : Author
Fernando Brites
  • Function : Author
Gerard Bolbach
  • Function : Author
Emmanuel Gautier
  • Function : Author
Thierry Huby
  • Function : Author
Alain Carrie
  • Function : Author
Eric Bruckert
  • Function : Author
Maryse Guerin
Philippe Giral
  • Function : Author
Philippe Lesnik
  • Function : Author
Wilfried Le Goff
  • Function : Author
Isabelle Guillas
  • Function : Author
Anatol Kontush
  • Function : Author

Abstract

Background Low concentrations of high-density lipoprotein cholesterol (HDL-C) represent a well-established cardiovascular risk factor. Paradoxically, extremely high HDL-C levels are equally associated with elevated cardiovascular risk, resulting in the U-shape relationship of HDL-C with cardiovascular disease. Mechanisms underlying this association are presently unknown. We hypothesised that the capacity of high-density lipoprotein (HDL) to acquire free cholesterol upon triglyceride-rich lipoprotein (TGRL) lipolysis by lipoprotein lipase underlies the non-linear relationship between HDL-C and cardiovascular risk. Methods To assess our hypothesis, we developed a novel assay to evaluate the capacity of HDL to acquire free cholesterol (as fluorescent TopFluor® cholesterol) from TGRL upon in vitro lipolysis by lipoprotein lipase. Results When the assay was applied to several populations markedly differing in plasma HDL-C levels, transfer of free cholesterol was significantly decreased in low HDL-C patients with acute myocardial infarction (−45%) and type 2 diabetes (–25%), and in subjects with extremely high HDL-C of >2.59 mmol/L (>100 mg/dL) (−20%) versus healthy normolipidaemic controls. When these data were combined and plotted against HDL-C concentrations, an inverse U-shape relationship was observed. Consistent with these findings, animal studies revealed that the capacity of HDL to acquire cholesterol upon lipolysis was reduced in low HDL-C apolipoprotein A-I knock-out mice and was negatively correlated with aortic accumulation of [ 3 H]-cholesterol after oral gavage, attesting this functional characteristic as a negative metric of postprandial atherosclerosis. Conclusions Free cholesterol transfer to HDL upon TGRL lipolysis may underlie the U-shape relationship between HDL-C and cardiovascular disease, linking HDL-C to triglyceride metabolism and atherosclerosis.

Dates and versions

hal-04004325 , version 1 (24-02-2023)

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Ma Feng, Maryam Darabi, Emilie Tubeuf, Aurélie Canicio, Marie Lhomme, et al.. Free cholesterol transfer to high-density lipoprotein (HDL) upon triglyceride lipolysis underlies the U-shape relationship between HDL-cholesterol and cardiovascular disease. European Journal of Preventive Cardiology, 2020, 27 (15), pp.1606-1616. ⟨10.1177/2047487319894114⟩. ⟨hal-04004325⟩
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