Gomaraschi_2017_J.Lipid.Res_58_994

Reference

Title : Depletion in LpA-I:A-II particles enhances HDL-mediated endothelial protection in familial LCAT deficiency - Gomaraschi_2017_J.Lipid.Res_58_994
Author(s) : Gomaraschi M , Ossoli A , Castelnuovo S , Simonelli S , Pavanello C , Balzarotti G , Arca M , Di Costanzo A , Sampietro T , Vaudo G , Baldassarre D , Veglia F , Franceschini G , Calabresi L
Ref : J Lipid Res , 58 :994 , 2017
Abstract :

The aim of this study was to evaluate the vasoprotective effects of HDL isolated from carriers of LCAT deficiency, which are characterized by a selective depletion of LpA-I:A-II particles and predominance of prebeta migrating HDL. HDLs were isolated from LCAT-deficient carriers and tested in vitro for their capacity to promote NO production and to inhibit vascular cell adhesion molecule-1 (VCAM-1) expression in cultured endothelial cells. HDLs from carriers were more effective than control HDLs in promoting eNOS activation with a gene-dose-dependent effect (PTrend = 0.048). As a consequence, NO production induced by HDL from carriers was significantly higher than that promoted by control HDL (1.63 +/- 0.24-fold vs. 1.34 +/- 0.07-fold, P = 0.031). HDLs from carriers were also more effective than control HDLs in inhibiting the expression of VCAM-1 (homozygotes, 65.0 +/- 8.6%; heterozygotes, 53.1 +/- 7.2%; controls, 44.4 +/- 4.1%; PTrend = 0.0003). The increased efficiency of carrier HDL was likely due to the depletion in LpA-I:A-II particles. The in vitro findings might explain why carriers of LCAT deficiency showed flow-mediated vasodilation and plasma-soluble cell adhesion molecule concentrations comparable to controls, despite low HDL-cholesterol levels. These results indicate that selective depletion of apoA-II-containing HDL, as observed in carriers of LCAT deficiency, leads to an increased capacity of HDL to stimulate endothelial NO production, suggesting that changes in HDL apolipoprotein composition may be the target of therapeutic interventions designed to improve HDL functionality.

PubMedSearch : Gomaraschi_2017_J.Lipid.Res_58_994
PubMedID: 28351888
Gene_locus related to this paper: human-LCAT

Citations formats

Gomaraschi M, Ossoli A, Castelnuovo S, Simonelli S, Pavanello C, Balzarotti G, Arca M, Di Costanzo A, Sampietro T, Vaudo G, Baldassarre D, Veglia F, Franceschini G, Calabresi L (2017)
Depletion in LpA-I:A-II particles enhances HDL-mediated endothelial protection in familial LCAT deficiency
J Lipid Res 58 :994

Gomaraschi M, Ossoli A, Castelnuovo S, Simonelli S, Pavanello C, Balzarotti G, Arca M, Di Costanzo A, Sampietro T, Vaudo G, Baldassarre D, Veglia F, Franceschini G, Calabresi L (2017)
J Lipid Res 58 :994