Deposition of free cholesterol in the blood vessels of patients with coronary artery disease: a possible novel mechanism for atherogenesis.
A cholesterol-rich nanoemulsion (LDE) that mimics the composition of low-density lipoprotein (LDL) acquires apoE in the plasma and is taken-up by the cells by LDL receptors. In this study, to verify whether free cholesterol (FC) and the cholesteryl ester (CE) components of LDL are taken-up differently by the vessels. LDE labeled with (3)H-cholesterol and (14)C-cholesteryl oleate was injected into 20 coronary artery disease patients 24 h before a scheduled myocardial coronary artery bypass grafting. The plasma kinetics of both radiolabels was determined from plasma samples collected over 24 h, and fragments of vessels discarded during surgery were collected and analyzed for radioactivity. LDE FC was removed faster than CE. The radioactive counting of LDE CE was greater than that of LDE FC in the blood, but the uptake of FC was markedly greater than that of CE in all fragments: fivefold greater in the aorta (p = 0.04), fourfold greater in the internal thoracic artery (p = 0.03), tenfold greater in the saphenous vein (p = 0.01) and threefold in the radial artery (p = 0.05). In conclusion, the greater removal from plasma of FC compared with CE and the remarkably greater vessel tissue uptake of FC compared with CE suggests that, in the plasma, FC dissociates from the nanoemulsion particles and precipitates in the vessels. Considering LDE as an artificial nanoemulsion model for LDL, our results suggest that dissociation of FC from lipoprotein particles and deposition in the vessel wall may play a role as an independent mechanism in atherogenesis.
Couto
Ricardo D
RD
Lipid Metabolism Laboratory and the Surgical Division, The Heart Institute (INCOR) of the Medical School Hospital, University of São Paulo, Sao Paulo, Brazil.
Dallan
Luís A O
LA
Lisboa
Luiz A F
LA
Mesquita
Carlos H
CH
Vinagre
Carmen G C
CG
Maranhão
Raul C
RC
D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism; D002784:Cholesterol / Q000097:blood*; D002788:Cholesterol Esters / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood* / Q000378:metabolism; D004655:Emulsions; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry
D002788:Cholesterol Esters; D004655:Emulsions; D002784:Cholesterol