Aim of the 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. HDL were isolated from LCAT deficient carriers and tested in vitro for their capacity to promote NO production and to inhibit VCAM-1 expression in cultured endothelial cells. HDL from carriers were more effective than control HDL 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 vs 1.34±0.07 fold, P=0.031). HDL from carriers were also more effective than control HDL 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-C 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.
Depletion in LpA-I:A-II particles enhances HDL-mediated endothelial protection in familial LCAT deficiency / M. Gomaraschi, A. Ossoli, S. Castelnuovo, S. Simonelli, C. Pavenello, G. Balzarotti, M. Arca, A. Di Costanzo, T. Sampietro, G. Vaudo, D. Baldassarre, F. Veglia, G. Franceschini, L. Calabresi. - In: JOURNAL OF LIPID RESEARCH. - ISSN 0022-2275. - 58:5(2017), pp. 994-1001.
|Titolo:||Depletion in LpA-I:A-II particles enhances HDL-mediated endothelial protection in familial LCAT deficiency|
GOMARASCHI, MONICA (Primo)
OSSOLI, ALICE FEDERICA (Secondo)
FRANCESCHINI, GUIDO (Penultimo)
CALABRESI, LAURA (Corresponding)
|Parole Chiave:||endothelium; nitric oxide; apolipoprotein A-II; high density lipoprotein; lecithin:cholesterol acyltransferase|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||2017|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1194/jlr.P072371|
|Appare nelle tipologie:||01 - Articolo su periodico|
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