info:eu-repo/semantics/article
Phospholipid transfer to high-density lipoprotein (HDL) upon triglyceride lipolysis is directly correlated with HDL-cholesterol levels and is not associated with cardiovascular risk
Fecha
2021-05Registro en:
Ma, Feng; Darabi, Maryam; Lhomme, Marie; Tubeuf, Emilie; Canicio, Aurélie; et al.; Phospholipid transfer to high-density lipoprotein (HDL) upon triglyceride lipolysis is directly correlated with HDL-cholesterol levels and is not associated with cardiovascular risk; Elsevier Ireland; Atherosclerosis; 324; 5-2021; 1-8
0021-9150
CONICET Digital
CONICET
Autor
Ma, Feng
Darabi, Maryam
Lhomme, Marie
Tubeuf, Emilie
Canicio, Aurélie
Brerault, Jean
Medadje, Narcisse
Rached, Fabiana
Lebreton, Sandrine
Frisdal, Eric
Brites, Fernando Daniel
Serrano, Carlos
Santos, Raul
Gautier, Emmanuel
Huby, Thierry
El Khoury, Petra
Carrié, Alain
Abifadel, Marianne
Bruckert, Eric
Guerin, Maryse
Couvert, Philippe
Giral, Philippe
Lesnik, Philippe
Le Goff, Wilfried
Guillas, Isabelle
Kontush, Anatol
Resumen
Background and aims: While low concentrations of high-density lipoprotein-cholesterol (HDL-C) represent a well-established cardiovascular risk factor, extremely high HDL-C is paradoxically associated with elevated cardiovascular risk, resulting in the U-shape relationship with cardiovascular disease. Free cholesterol transfer to HDL upon lipolysis of triglyceride-rich lipoproteins (TGRL) was recently reported to underlie this relationship, linking HDL-C to triglyceride metabolism and atherosclerosis. In addition to free cholesterol, other surface components of TGRL, primarily phospholipids, are transferred to HDL during lipolysis. It remains indeterminate as to whether such transfer is linked to HDL-C and cardiovascular disease. Methods and results: When TGRL was labelled with fluorescent phospholipid 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI), time- and dose-dependent transfer of DiI to HDL was observed upon incubations with lipoprotein lipase (LPL). The capacity of HDL to acquire DiI was decreased by −36% (p<0.001) in low HDL-C patients with acute myocardial infarction (n = 22) and by -95% (p<0.001) in low HDL-C subjects with Tangier disease (n = 7), unchanged in low HDL-C patients with Type 2 diabetes (n = 17) and in subjects with high HDL-C (n = 20), and elevated in subjects with extremely high HDL-C (+11%, p<0.05) relative to healthy normolipidemic controls. Across all the populations combined, HDL capacity to acquire DiI was directly correlated with HDL-C (r = 0.58, p<0.001). No relationship of HDL capacity to acquire DiI with both overall and cardiovascular mortality obtained from epidemiological studies for the mean HDL-C levels observed in the studied populations was obtained. Conclusions: These data indicate that the capacity of HDL to acquire phospholipid from TGRL upon LPL-mediated lipolysis is proportional to HDL-C and does not reflect cardiovascular risk in subjects widely differing in HDL-C levels.