Objective: Carriers of apolipoprotein A-IMilano (A-IM), the R173C mutant of apoA-I, are protected against cardiovascular diseases despite very low HDL-cholesterol (HDL-C) levels and hypertriglyceridemia. Aim of the present study was to investigate the endothelial function of A-IM carriers, since low HDL-C levels have been associated with features of endothelial dysfunction. Methods and Results: Plasma concentrations of soluble cell adhesion molecules (sCAMs), and forearm arterial compliance during reactive hyperemia were evaluated in 21 A-IM carriers, 21 healthy subjects with low HDL-C, and 42 controls. Low HDL-C subjects had significantly higher plasma sCAM levels than controls; on the contrary, no differences were detected between A-IM carriers and controls, indicating that HDL from A-IM carriers may be more efficient than control HDL in inhibiting endothelial CAM expression. Thus, HDL were isolated from 6 A-IM carriers and 6 controls, and their ability to inhibit VCAM-1 expression was tested in endothelial cells. HDL from A-IM carriers were twice effective than control HDL in reducing TNFalpha-induced VCAM-I expression, and the inhibition occurred at a transcriptional level, as demonstrated by RT-PCR. Interestingly, no differences in arterial compliance during reactive hyperemia were detected between A-IM carriers and controls. Conclusion: Despite very low HDL-C levels, A-IM carriers do not display features of endothelial dysfunction, such as the increase of circulating sCAM levels and the impairment of arterial compliance, probably because of a superior ability of A-IM containing HDL to protect the endothelium.
Normal endothelial function in carriers of the apolipoprotein A-1milano mutant despite low HDL-cholesterol levels / M. Gomaraschi, D. Baldassarre, M. Amato, S. Eligini, C.R. Sirtori, G. Franceschini, L. Calabresi. - In: ATHEROSCLEROSIS SUPPLEMENTS. - ISSN 1567-5688. - 7:3(2006), pp. 152-152. ((Intervento presentato al 14. convegno International Symposium on Atherosclerosis tenutosi a Roma nel 2006 [10.1016/S1567-5688(06)80599-4].
Normal endothelial function in carriers of the apolipoprotein A-1milano mutant despite low HDL-cholesterol levels
M. GomaraschiPrimo
;D. BaldassarreSecondo
;S. Eligini;C.R. Sirtori;G. FranceschiniPenultimo
;L. CalabresiUltimo
2006
Abstract
Objective: Carriers of apolipoprotein A-IMilano (A-IM), the R173C mutant of apoA-I, are protected against cardiovascular diseases despite very low HDL-cholesterol (HDL-C) levels and hypertriglyceridemia. Aim of the present study was to investigate the endothelial function of A-IM carriers, since low HDL-C levels have been associated with features of endothelial dysfunction. Methods and Results: Plasma concentrations of soluble cell adhesion molecules (sCAMs), and forearm arterial compliance during reactive hyperemia were evaluated in 21 A-IM carriers, 21 healthy subjects with low HDL-C, and 42 controls. Low HDL-C subjects had significantly higher plasma sCAM levels than controls; on the contrary, no differences were detected between A-IM carriers and controls, indicating that HDL from A-IM carriers may be more efficient than control HDL in inhibiting endothelial CAM expression. Thus, HDL were isolated from 6 A-IM carriers and 6 controls, and their ability to inhibit VCAM-1 expression was tested in endothelial cells. HDL from A-IM carriers were twice effective than control HDL in reducing TNFalpha-induced VCAM-I expression, and the inhibition occurred at a transcriptional level, as demonstrated by RT-PCR. Interestingly, no differences in arterial compliance during reactive hyperemia were detected between A-IM carriers and controls. Conclusion: Despite very low HDL-C levels, A-IM carriers do not display features of endothelial dysfunction, such as the increase of circulating sCAM levels and the impairment of arterial compliance, probably because of a superior ability of A-IM containing HDL to protect the endothelium.File | Dimensione | Formato | |
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