The effect of large unilamellar vesicles on vascular function in patients with coronary atherosclerosis.
OBJECTIVE
To evaluate the effect of large unilamellar vesicles (LUVs) infusion on endothelial function. Low-density lipoprotein (LDL) lowering, particularly with statins, results in rapid attenuation of endothelial dysfunction and decreases cardiovascular events. Unique methods of removing cholesterol from the vessel wall are being developed. The effect of LUVs on endothelial function has not been evaluated in humans.


METHODS
75 subjects (mean age 61+/-10 years) with established vascular disease were randomized to receive either 2g, 8 g or matching placebo of LUVs as a weekly intravenous bolus infusion for 4 consecutive weeks. Brachial artery flow-mediated dilation (FMD) and nitroglycerin-mediated dilation was measured at baseline and 1 week after the last infusion. The primary study outcome was the change from baseline in FMD in the active therapy groups combined. Predefined secondary end-points included nitroglycerin-mediated dilation and safety.


RESULTS
Active therapy (combined 2g+8 g treatment groups, n=49) did not result in a change in FMD, but did improve nitroglycerin dilation (p<0.05). However, a beneficial effect on both FMD (10.2+/-5.7% vs. 11.8+/-5.5%) and nitroglycerin-mediated dilation (18.1+/-9.3% vs. 21.2+/-8.7%, both p<0.05) was seen in the 2-g group. Infusion of the 8-g dose resulted in significantly higher levels of unesterified cholesterol compared with the other groups during the study period (p<0.01).


CONCLUSIONS
The current study demonstrated no overall effect of LUVs on FMD, however nitroglycerin-mediated dilation was improved. Further studies are required to clarify if there is a dose-dependent effect of this therapy and what its role is in subjects with atherosclerosis.
Anderson
Todd
T
Department of Cardiac Sciences and the Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, Canada. todd.anderson@calgaryhealthregion.ca
Charbonneau
Francois
F
Chan
Sammy
S
Lonn
Eva
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism; D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D004727:Endothelium / Q000473:pathology; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000494:pharmacology; D010919:Placebos; D016896:Treatment Outcome
D008077:Lipoproteins, LDL; D010919:Placebos; D002784:Cholesterol; D005996:Nitroglycerin