title: Novel Therapy for Atherosclerosis Using Recombinant Immunotoxin Against Folate Receptor β-Expressing Macrophages.
abstract: BACKGROUND
  Folate receptor β (FRβ) is induced during macrophage activation. A recombinant immunotoxin consisting of the truncated Pseudomonas exotoxin A (PE38) conjugated to an anti-FRβ antibody (anti-FRβ-PE38) has been reported to kill activated macrophages in inflammatory diseases. To elucidate the effect of an immunotoxin targeting FRβ on atherosclerosis, we determined the presence of FRβ-expressing macrophages in atherosclerotic lesions and administered the FRβ immunotoxin in apolipoprotein E-deficient mice.
  
  
  RESULTS
  The FRβ-expressing macrophages were observed in atherosclerotic lesions of apolipoprotein E-deficient mice. At 15 or 35 weeks of age, the apolipoprotein E-deficient mice were divided into 3 groups and were intravenously administered 0.1 mg/kg of anti-FRβ-PE38 (immunotoxin group), 0.1 mg/kg of PE38 (toxin group), or 0.1 mL of saline (control group) every 3 days, for a total of 5 times for each age group. The mice were analyzed at 21 or 41 weeks of age. Treatment with the immunotoxin resulted in 31% and 22% reductions in atherosclerotic lesions of the 21- and 41-week-old mice, respectively (P<0.05). Administration of immunotoxin reduced the numbers of FRβ- and tumor necrosis factor-α-expressing macrophages, reduced cell proliferation, and increased the number of apoptotic cells (P<0.05). Real-time polymerase chain reaction demonstrated that the expression of FRβ and tumor necrosis factor-α mRNA was significantly decreased in the immunotoxin group (P<0.05).
  
  
  CONCLUSIONS
  These results suggest that FRβ-expressing macrophages exist in the atherosclerotic lesions of apolipoprotein E-deficient mice and that FRβ immunotoxin administration reduces the progression of atherosclerotic lesions in younger and older individuals. The recombinant FRβ immunotoxin targeting activated macrophages could provide a novel therapeutic tool for atherosclerosis. (J Am Heart Assoc. 2012;1:e003079 doi: 10.1161/JAHA.112.003079.).
authors.affiliation: Department of Cardiovascular, Respiratory, and Metabolic Medicine, Kagoshima University,  Kagoshima, Japan (Y.F., M.M., Y.A., N.H., T. Miyauchi, Y.I., T.S., K.I., C.T.).
authors.forename: Yuko
authors.initials: Y
authors.lastname: Furusho
authors.forename: Masaaki
authors.initials: M
authors.lastname: Miyata
authors.forename: Takami
authors.initials: T
authors.lastname: Matsuyama
authors.forename: Taku
authors.initials: T
authors.lastname: Nagai
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Akasaki
authors.forename: Narisato
authors.initials: N
authors.lastname: Hamada
authors.forename: Takahiro
authors.initials: T
authors.lastname: Miyauchi
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shirasawa
authors.forename: Kanako
authors.initials: K
authors.lastname: Ide
authors.forename: Chuwa
authors.initials: C
authors.lastname: Tei
keywords: antibodies; atherosclerosis; inflammation; plaque; receptors