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Small, dense HDL3 particles attenuates apoptosis in endothelial cells: Pivotal role of apolipoprotein A-I.

Abstract : Abstract Plasma high-density lipoprotein (HDL) protect endothelial cells against apoptosis induced by oxidatively modified low-density lipoprotein (oxLDL). The specific component(s) of HDL implicated in such cytoprotection remain(s) to be identified. Human microvascular endothelial cells (HMEC-1) were incubated with mildly oxLDL in the presence or absence of each of five physicochemically-distinct HDL subpopulations fractionated from normolipidemic human plasma (n=7) by isopycnic density gradient ultracentrifugation. All HDL subfractions protected HMEC-1 against oxLDL-induced primary apoptosis as revealed by nucleic acid staining, annexin V binding, quantitative DNA fragmentation, inhibition of caspase-3 activity, and reduction of cytoplasmic release of cytochrome c and apoptosis-inducing factor. Small, dense HDL3c displayed twofold superior intrinsic cytoprotective activity (as determined by mitochondrial dehydrogenase activity) relative to large, light HDL2b on a per particle basis (p<0.05). Equally, all HDL subfractions attenuated intracellular generation of reactive oxygen species (ROS); such antioxidative activity diminished from HDL3c to HDL2b. The HDL protein moiety, in which apolipoprotein A-I (apoA-I) predominated, accounted for approximately 70% of HDL antiapoptotic activity. Furthermore, HDL reconstituted with apoA-I, cholesterol and phospholipid potently protected HMEC-1 from apoptosis. By contrast, modification of the content of sphingosine-1-phosphate in HDL did not significantly alter cytoprotection. We conclude that small, dense, lipid-poor HDL3 potently protect endothelial cells from primary apoptosis and intracellular ROS generation induced by mildly oxLDL, and that apoA-I is pivotal to such protection.
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Contributor : Marie Francoise Simon Connect in order to contact the contributor
Submitted on : Thursday, August 20, 2009 - 11:27:08 AM
Last modification on : Wednesday, June 1, 2022 - 5:23:43 AM

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Juliana A. de Souza, Cecile Vindis, Anne Nègre-Salvayre, Kerry-Anne Rye, Martine Couturier, et al.. Small, dense HDL3 particles attenuates apoptosis in endothelial cells: Pivotal role of apolipoprotein A-I.. Journal of Cellular and Molecular Medicine, Wiley Open Access, 2009, 14 (3), pp.608-620 ⟨10.1111/j.1582-4934.2009.00713.x⟩. ⟨inserm-00410382⟩



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