Macrophage hemoglobin scavenger receptor CD163 is functionally linked to heme oxygenase‐1 and ferritin expression in human diabetic atherosclerotic plaques

Background The macrophage hemoglobin scavenging receptor CD163 plays a major role in the clearance of hemoglobin (Hb) released from lysed red blood cells after intraplaque hemorrhage (IPH). We hypothesize that impairment in CD163 expression may alter HO‐1 and ferritin defense mechanism in the clearance of Hb in diabetic (DM) plaques inducing atherothrombosis. Methods Human DM atherosclerotic plaques (33) and no‐DM plaques (49) were characterized using H&E. The macrophage (CD68) and CD163 protein expressions were quantified by double label immunochemistry and gene expression in serial sections by real time PCR. The HO‐1 and ferritin protein expression was graded by immunohistochemistry. Results The mean percentage of macrophages expressing CD163 was significantly decreased in DM plaques (DM 26.2 % ± 2 vs No‐DM 66.9 % ± 2, p=0.0001). The CD163 and HO‐1 mRNA expressions were down regulated in DM (DM 0.0689±0.017 vs No‐DM 0.3078±0.055, p=0.002, and DM 0.002±0.0006 vs No‐DM 0.0369±0.012, P =0.005) respectively. The protein expression of ferritin was also decreased in DM plaques (DM 0.7±0.1 vs no‐DM 2.6±0.2, p=0.0001). Conclusion CD163 may have a functional role in the induction of HO‐1 and ferritin expression. Thus, impairment in CD163 expression may alter HO‐1 and ferritin defense mechanism leading to atherothrombosis in DM plaques.