Differing patterns of cholesterol accumulation and 3-H-cholesterol influx in areas of the cholesterol-fed pig aorta identified by evans blue dye.

In this study we have examined the possible focal and regional nature of aortic cholesterol accumulation in pigs receiving a cholesterol-containing diet for 6 to 16 weeks. Using uptake of the protein-binding azo dye Evans Blue as a marker for focal areas of increased aortic endothelial permeability in viva, we have found a significantly greater intimal accumulation of cholesterol in areas of dye uptake (blue areas) than in contiguous areas of the thoracic aorta showing no dye uptake (white areas). This focal difference in cholesterol accumulation was confined to the intima alone, and was not observed in either intima-media, or medial preparations. No measurable cholesterol accumulation was observed in the intima of blue relative to white areas in the absence of cholesterol feeding. [3H]cholesterol was administered 72 hr before death to four pigs receiving a cholesterol diet for 6 weeks. Unesterified cholesterol radioactivity was found to be 60-70s of the total activity in intimal or medial tissue. For each site studied (thoracic blue, thoracic white, and abdominal white), intimal cholesterol radioactivity was significantly greater than in the underlying media. Unesterified and esterified cholesterol radioactivity in intimal blue areas was significantly greater than the respective activities in the intima from thoracic white or abdominal white areas. Cholesterol accumulation in the intima, but not in the intima-media alone, was found to exhibit a regional difference as well, with significantly greater accumulation in the thoracic than abdominal aortic segments. This regional pattern was also reflected in the “H unesterified and esterified cholesterol activity in the intimal preparations from the thoracic and abdominal aortic segments. This study has shown that aortic cholesterol accumulation is not homogeqeous. The regional and focal difference in cholesterol accumulation observed may reflect local hemodynamic effects. The implications of these findings in terms of endothelial permeability to lipoproteins, and the pathogenesis of atherosclerois are discussed.