Experimental protocol and plasma cholesterol levels. Rabbits were fed a high-fat diet for 4 weeks, containing the indicated percentages of cholesterol. Rabbits then underwent neck surgery with bilateral common carotid artery infusions of DMEM to help initiate atherosclerosis development. Plasma cholesterol was measured at this time and every 2 weeks thereafter. From the end of week 4 through the time of gene transfer (GT), dietary cholesterol was adjusted according to a sliding scale with a goal of maintaining plasma cholesterol in the range of 200–800 mg/dL (gray horizontal bar). Most of the rabbits (~ 80%) underwent gene transfer during week 28. Due to scheduling issues, ~ 20% were treated during week 29. Gene transfer in one rabbit was delayed until week 31 due to an anesthetic complication. Gene transfer included infusion of HDAdNull and HDAdApoAI in contralateral carotids, with the side for each vector randomized. After gene transfer, rabbits were switched to normal chow and carotids removed 3 days or 7 weeks later.