Erythrophagocytosis and iron deposition in atherosclerotic lesions.

Iron deposition has been shown to be prominent in atherosclerotic lesions. However, the source of iron accumulated in arterial walls is unclear. In present report, we provide the histological evidence to demonstrate the localization of erythrocytes in atherosclerotic lesions from experimental animals. As revealed by scanning and transmission electron microscopy, the circulating erythrocytes were found to be present in intima of atherosclerotic aortas from apoE-deficient mice. These erythrocytes appeared to be readily phagocytosed by macrophages in lesions. The erythrophagocytosis was also evident in lesions from cholesterol-fed rabbits. Furthermore, the iron deposition was detectable in the region with erythrocytes. When the aortic sections of humans and apoE-deficient mice were immunostained with specific antibody to hemoglobin, it was clearly shown that the positive stain was detectable in macrophage-derived foam cells. Immunostaining of serial sections with specific antibodies to heme oxygenase-1 (HO-1) and ferritin further demonstrated the colocalization of HO-1 and ferritin in area with positive immunoreactivity for hemoglobin. Likewise, Perls' reaction revealed the positive iron stain in the same region. Collectively, these results suggest that hemoglobin/heme released from the phagocytosed erythrocytes may contribute to at least part of iron deposited in atherosclerotic lesions.