title: Detection and photodynamic therapy of inflamed atherosclerotic plaques in the carotid artery of rabbits.
abstract: 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 (635nm at 50J/cm(2)) 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 2h 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 4week after PDT, the plaque macrophage content decreased by 56% at 1week and 64% at 4week respectively, the smooth muscle cells (SMCs) was depleted by 24% at 1week (P<0.05) and collagen content increased by 44% at 4week (P<0.05). It should be pointed out that the SMC content increased by 18% after PDT at 4week compared with that at 1week (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.
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital, Harbin Medical University, Harbin 150086, PR China.
authors.forename: Chenghai
authors.initials: C
authors.lastname: Peng
authors.forename: Yuanshi
authors.initials: Y
authors.lastname: Li
authors.forename: Huijuan
authors.initials: H
authors.lastname: Liang
authors.forename: Jiali
authors.initials: J
authors.lastname: Cheng
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.forename: Zhitao
authors.initials: Z
authors.lastname: Li
authors.forename: Fengping
authors.initials: F
authors.lastname: Wang
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Guo
authors.forename: Zhen
authors.initials: Z
authors.lastname: Tian
authors.forename: Liming
authors.initials: L
authors.lastname: Yang
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Wenwu
authors.initials: W
authors.lastname: Cao
mesh_terms: D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D010587:Phagocytosis / Q000187:drug effects / Q000528:radiation effects; D010778:Photochemotherapy / Q000379:methods*; D058226:Plaque, Atherosclerotic / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D011524:Protoporphyrins / Q000378:metabolism; D011817:Rabbits; D013050:Spectrometry, Fluorescence
chemical_list: D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX