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 preβ 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

Gomaraschi M, Ossoli A, Castelnuovo S, Simonelli S, Balzarotti G, Arca M, Di Costanzo A, Sampietro T, Vaudo G, Veglia F, Franceschini G, Calabresi L / Gomaraschi, M; Ossoli, A; Castelnuovo, S; Simonelli, S; Balzarotti, G; Arca, M; Di Costanzo, A; Sampietro, T; Vaudo, G; Veglia, F; Franceschini, G; Calabresi, L. - In: JOURNAL OF LIPID RESEARCH. - ISSN 0022-2275. - 58:5(2017), pp. 994-1001. [10.1194/jlr.P072371]

Gomaraschi M, Ossoli A, Castelnuovo S, Simonelli S, Balzarotti G, Arca M, Di Costanzo A, Sampietro T, Vaudo G, Veglia F, Franceschini G, Calabresi L

Arca M
Writing – Review & Editing
;
Di Costanzo A
Membro del Collaboration Group
;
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 preβ 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
2017
LCAT deficiency; genetics; apoproteins; apoAI; endothelium; HDL
01 Pubblicazione su rivista::01a Articolo in rivista
Gomaraschi M, Ossoli A, Castelnuovo S, Simonelli S, Balzarotti G, Arca M, Di Costanzo A, Sampietro T, Vaudo G, Veglia F, Franceschini G, Calabresi L / Gomaraschi, M; Ossoli, A; Castelnuovo, S; Simonelli, S; Balzarotti, G; Arca, M; Di Costanzo, A; Sampietro, T; Vaudo, G; Veglia, F; Franceschini, G; Calabresi, L. - In: JOURNAL OF LIPID RESEARCH. - ISSN 0022-2275. - 58:5(2017), pp. 994-1001. [10.1194/jlr.P072371]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1195084
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