Detection and photodynamic therapy of inflamed atherosclerotic plaques in the carotid artery of rabbits

Photodynamic therapy (PDT) has been applied in the treatment of artery restenosis following balloon injury. This study aimed to detect the accumulation of 5-aminolevulinic acid (ALA)-derived protoporphyrin IX (PpIX) in inflamed atherosclerotic plaque in rabbit model and evaluate the efficacy of PDT. The inflamed atherosclerotic plaque in the common carotid artery was produced by combination of balloon denudation injury and high cholesterol diet. After intravenous administration of ALA, the fluorescence of PpIX in plaque was detected. At the peak time, the correlation between the fluorescence intensity of PpIX and the macrophage infiltration extent in plaque was analyzed. Subsequently, PDT (635 nm at 50 J/cm2) on the atherosclerotic plaques (n = 48) was performed and its effect was evaluated by histopathology and immunohistochemistry. The fluorescence intensity of PpIX in the plaque reached the peak 2 h after injection and was 12 times stronger than that of adjacent normal vessel segment, and has a positive correlation with the macrophage content (r = 0.794, P < 0.001). Compared with the control group, the plaque area was reduced by 59% (P < 0.001) at 4 week after PDT, the plaque macrophage content decreased by 56% at 1 week and 64% at 4 week respectively, the smooth muscle cells (SMCs) was depleted by 24% at 1 week (P < 0.05) and collagen content increased by 44% at 4 week (P < 0.05). It should be pointed out that the SMC content increased by 18% after PDT at 4 week compared with that at 1 week (P < 0.05). Our study demonstrated that the ALA-derived PpIX can be detected to reflect the macrophage content in the plaque. ALA mediated PDT could reduce macrophage content and inhibit plaque progression, indicating a promising approach to treat inflamed atherosclerotic plaques.