Metabolite concentration gradients in the arterial wall of experimental atherosclerosis.

Development of intimal necrosis is characteristic of advanced atherosclerotic lesions. In order to study metabolic alterations preceding cellular death, the concentration gradients of glucose, glycogen, ATP, and lactate were measured within the walls of rabbit carotid arteries which were transmurally stimulated by dc impulses. This experimental model allows the induction of lipid-free intimal myocyte proliferations usually void of necrosis and, under additional hypercholesterolemia, typical lipid-laden atheromas, which become necrotic after 5-6 weeks of stimulation. Frozen samples (1 X 3 mm2) obtained from normal arterial wall and from both types of plaques as well as from spontaneously occurring aortic lesions of the hypercholesterolemic rabbits were cut in consecutive slices (10 microns thick) parallel to the luminal surface from the intima toward the adventitia. Compared with normal media, the results show that in the neointima the concentrations of glucose and glycogen decreased whereas that of lactate increased, independent of whether or not hypercholesterolemia was induced. The ATP concentration in lipid-free plaques was comparable with that in normal media, but strongly decreased in lesions which developed in combination with hypercholesterolemia. These observations support the view that in the initial stages of plaque growth, the intimal cells reveal an increased energy turnover leading to a decreased glycogen content. The development of necrosis, however, seems to involve additional events associated with a decrease in ATP, obviously depending on the effects of lipids or lipoproteins in the cells of the arterial wall.