Neopterin and 7,8-dihydroneopterin are generated within atherosclerotic plaques

Abstract

Abstract Plasma neopterin correlates with the level of cardiovascular disease. Neopterin is the oxidation product of 7,8-dihydroneopterin, which is released by γ-interferon-stimulated macrophages. 7,8-Dihydroneopterin is a potent antioxidant, which inhibits lipid oxidation, macrophage cell death and scavenger receptor CD36 expression. The concentration of neopterin within atherosclerotic plaques was measured in tissue removed from carotid and femoral arteries. The excised plaques were cut into 3-mm-thick sections, and each section was analysed for neopterin, total neopterin, cholesterol, lipid peroxides, α-tocopherol and protein-bound 3,4-dihydroxyphenylalanine. Selected plaques were placed in tissue culture, and the media was analysed for 7,8-dihydroneopterin and neopterin release. Total neopterin levels ranged from 14 to 18.8 nmol/g of tissue. Large ranges of values were seen both within the same plaque and between plaques. No correlation between neopterin and any of the other analytes was observed, nor was there any significant trend in levels along the length of the plaques. γ-Interferon stimulation of cultured plaque generated total neopterin concentrations from 1 to 4 nmol/(g 24 h). The level of 7,8-dihydroneopterin generated within the plaque was within the range that inhibits lipid oxidation. The data show that atherosclerotic plaques are extremely dynamic in biochemistry and are the likely source of the plasma 7,8-dihydroneopterin and neopterin.