Carriers of the apolipoprotein A-IMilano (apoA-IM) mutant have very low plasma HDL-cholesterol (HDL-C) levels but do not show any history of premature cardiovascular disease nor any evidence of preclinical vascular disease. HDL are believed to prevent the development of endothelial dysfunction, which may well contribute to HDL-mediated atheroprotection. Whether the low HDL level of apoA-IM carriers is associated with impaired endothelial function is presently unknown. In the present study, the changes of forearm arterial compliance (FAC) during reactive hyperemia and the plasma concentration of soluble cell adhesion molecules (sCAMs) were evaluated in 21 adult apoA-IM carriers, 21 age-gender matched non affected relatives (Controls), and 21 healthy subjects with low HDL-C (Low-HDL). The average plasma HDL-C and apoA-1 levels of apoA-IM carriers were remarkably lower than those of Controls, and significantly lower than those of Low-HDL subjects. In the apoA-IM carriers, the percent change of FAC during reactive hyperemia was two-fold greater than in low-HDL subjects and remarkably similar to that of Controls. Plasma sCAM levels were similar in apoA-IM carriers and Controls, but greater in Low-HDL subjects. When incubated with endothelial cells, HDL isolated from apoA-IM carriers were more effective than HDL from Control and Low-HDL subjects in stimulating endothelial NO synthase expression and activation, and in down-regulating TNF-induced VCAM-1 expression. Thus, despite the very low HDL levels, the apoA-IM carriers do not display typical features of impaired endothelial function because of an improved activity of A-1M HDL in maintaining endothelial cell homeostasis.

NORMAL ENDOTHELlAL FUNCTION DESPlTE LOW HDL-CHOLESTEROL LEVELS IN CARRIERS OF THE APOLIPOPROTEIN A-IMitano MUTANT / M. Gomaraschi, D. Baldassarre, M. Amato, S. Eligini, P. Conca, C. Sirtori, G. Franceschini, L. Calabresi. - In: NMCD. NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES. - ISSN 0939-4753. - 18:1(2007), pp. S12-S12. ((Intervento presentato al 21. convegno CONGRESSO NAZIONALE DELLA SOCIETÀ ITALIANA PER LO STUDIO DELL’ARTERIOSCLEROSI (SISA) tenutosi a Perugia nel 2007.

NORMAL ENDOTHELlAL FUNCTION DESPlTE LOW HDL-CHOLESTEROL LEVELS IN CARRIERS OF THE APOLIPOPROTEIN A-IMitano MUTANT

M. Gomaraschi
Primo
;
D. Baldassarre
Secondo
;
S. Eligini;C. Sirtori;G. Franceschini
Penultimo
;
L. Calabresi
Ultimo
2007

Abstract

Carriers of the apolipoprotein A-IMilano (apoA-IM) mutant have very low plasma HDL-cholesterol (HDL-C) levels but do not show any history of premature cardiovascular disease nor any evidence of preclinical vascular disease. HDL are believed to prevent the development of endothelial dysfunction, which may well contribute to HDL-mediated atheroprotection. Whether the low HDL level of apoA-IM carriers is associated with impaired endothelial function is presently unknown. In the present study, the changes of forearm arterial compliance (FAC) during reactive hyperemia and the plasma concentration of soluble cell adhesion molecules (sCAMs) were evaluated in 21 adult apoA-IM carriers, 21 age-gender matched non affected relatives (Controls), and 21 healthy subjects with low HDL-C (Low-HDL). The average plasma HDL-C and apoA-1 levels of apoA-IM carriers were remarkably lower than those of Controls, and significantly lower than those of Low-HDL subjects. In the apoA-IM carriers, the percent change of FAC during reactive hyperemia was two-fold greater than in low-HDL subjects and remarkably similar to that of Controls. Plasma sCAM levels were similar in apoA-IM carriers and Controls, but greater in Low-HDL subjects. When incubated with endothelial cells, HDL isolated from apoA-IM carriers were more effective than HDL from Control and Low-HDL subjects in stimulating endothelial NO synthase expression and activation, and in down-regulating TNF-induced VCAM-1 expression. Thus, despite the very low HDL levels, the apoA-IM carriers do not display typical features of impaired endothelial function because of an improved activity of A-1M HDL in maintaining endothelial cell homeostasis.
Settore BIO/14 - Farmacologia
2007
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/201493
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