Lipid Metabolism and Molecular Changes in Normal andAtherosclerotic Vessels

Objectives: a positive correlation between cholesterol esterification, acyl-CoA:cholesterol acyltransferase (ACAT), multidrug resistance (MDR1) gene expression and atherosclerotic lesions has been shown in human arteries. The objective of this study was to map the expression of MDR1, ACAT genes and the cholesteryl ester content in normal, atherosclerotic and varicose human vessels. Materials: vascular segments were obtained from seven cadaveric donors, 27 patients undergoing vascular surgery for severe atherosclerotic disease and 11 patients with saphenous vein varicosities. Methods: lipid analysis and RT-PCR of MDR1 and ACAT mRNAs were performed. Results: an increase in cholesteryl ester content and in ACAT and MDR1 expression was demonstrated in relation to the age in the arteries prone to atherosclerosis; this expression was maximal in arteries from symptomatic patients. In resistant arteries and in veins cholesteryl ester accumulation was rare and light, while ACAT and MDR1 expression was not related to the age of the subjects. Conclusions: the results showed that an increase in MDR1 and ACAT expression may be responsible for the accumulation of cholesteryl esters as well as for cell growth rate acceleration in vessel sites prone to atherosclerosis.