AORTIC PERMEABILITY TO LDL AS A PREDICTOR OF AORTIC CHOLESTEROL ACCUMULATION IN CHOLESTEROL-FED RABBITS

The aim of this study was to investigate the possibility that the permeability characteristics of the arterial wall are related to the development of atheroscierosis. The in vivo regional variation of aortic permeability to iodinated human low density lipoprotein (LDL) in normal rabbits was compared with the regional variation in aortic cholesterol accumulation in cholesterol-fed rabbits. Aortas were divided into the aortic arch, thoracic aorta, and abdominal aorta, and each of these three parts was further subdivided into four segments of similar size. The permeability to LDL was 40 +/- 7 ml . cm-2- hr-1 (mean +/- SEM, n = 11) in the most proximal segment of the aortic arch and decreased throughout the length of the aorta to 3 +/- 1 nl . cm-2 . hr-1 in the most caudal segment of the abdominal aorta. In such normal rabbits the aortic cholesterol content was similar in all 12 arterial segments at 0.08 +/- 0.005 mumol/cm2 (mean +/- SEM, n = 3 x 12). Aortic cholesterol accumulation was determined in other rabbits with an average plasma cholesterol level of 32 +/- 1 mmol/I for 96 days; the cholesterol content in the most proximal segment of the aortic arch was 2.7 +/- 0.5 mumol/cm2 (mean +/- SEM, n = 11) and decreased with increasing distance from the heart to 0.17 +/- 0.03 mumol/cm2 in the most caudal segment of the abdominal aorta. Linear regression analysis showed a close positive association between the permeability to LDL of a given aortic segment and the cholesterol accumulation in that same aortic segment after cholesterol feeding (r2 = 0.96, p < 0.001). These results suggest that the aortic permeability to LDL is an important predictor for the development of atherosclerosis in cholesterol-fed rabbits.