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

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.
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Contributeur : LNC - université de Bourgogne Connectez-vous pour contacter le contributeur
Soumis le : mardi 13 février 2018 - 09:03:22
Dernière modification le : mercredi 23 novembre 2022 - 12:00:17

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Laurence Persègol, Maryam Darabi, Carolane Dauteuille, Marie Lhomme, Sandrine Chantepie, et al.. Small dense HDLs display potent vasorelaxing activity, reflecting their elevated content of sphingosine-1-phosphate. Journal of Lipid Research, 2018, 59 (1), pp.25 - 34. ⟨10.1194/jlr.M076927⟩. ⟨hal-01707695⟩



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