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Small dense HDLs display potent vasorelaxing activity, reflecting their elevated content of sphingosine-1-phosphate

Small dense HDLs display potent vasorelaxing activity, reflecting their elevated content of sphingosine-1-phosphate

Authors :
Perségol, Laurence
Darabi, Maryam
Dauteuille, Carolane
Lhomme, Marie
Chantepie, Sandrine
Rye, Kerry-Anne
Therond, Patrice
Chapman, M. John
Salvayre, Robert
Nègre-Salvayre, Anne
Lesnik, Philippe
Monier, Serge
Kontush, Anatol
Source :
Journal of Lipid Research; January 2018, Vol. 59 Issue: 1 p25-34, 10p
Publication Year :
2018

Abstract

The functional heterogeneity of HDL is attributed to its diverse bioactive components. We evaluated whether the vasodilatory effects of HDL differed across HDL subpopulations, reflecting their distinct molecular composition. The capacity of five major HDL subfractions to counteract the inhibitory effects of oxidized LDL on acetylcholine-induced vasodilation was tested in a rabbit aortic rings model. NO production, an essential pathway in endothelium-dependent vasorelaxation, was studied in simian vacuolating virus 40-transformed murine endothelial cells (SVECs). Small dense HDL3 subfractions displayed potent vasorelaxing activity (up to +31% vs. baseline, P< 0.05); in contrast, large light HDL2 did not induce aortic-ring relaxation when compared on a total protein basis. HDL3 particles were enriched with sphingosine-1-phosphate (S1P) (up to 3-fold vs. HDL2), with the highest content in HDL3b and -3c that concomitantly revealed the strongest vasorelaxing properties. NO generation was enhanced by HDL3c in SVECs (1.5-fold, P< 0.01), a phenomenon that was blocked by the S1P receptor antagonist, VPC 23019. S1P-enriched reconstituted HDL (rHDL) was a 1.8-fold (P< 0.01) more potent vasorelaxant than control rHDL in aortic rings. Small dense HDL3 particles displayed potent protective effects against oxidative stress-associated endothelium dysfunction, potentially reflecting their elevated content of S1P that might facilitate interaction with S1P receptors and ensuing NO generation.

Details

Language :
English
ISSN :
00222275 and 15397262
Volume :
59
Issue :
1
Database :
Supplemental Index
Journal :
Journal of Lipid Research
Publication Type :
Periodical
Accession number :
ejs44373363
Full Text :
https://doi.org/10.1194/jlr.M076927