title: Arrest of progression of pre-induced abdominal aortic aneurysm in apolipoprotein E-deficient mice by low level laser phototherapy.
abstract: OBJECTIVE
  Using non-invasive, high-frequency ultrasonography (HF-u/s), we showed that low-level laser phototherapy (LLL) inhibits de-novo formation of abdominal aortic aneurysms (AAA) in apolipoprotein-E-deficient (Apo-E(-/-)) mice. The current study tests the effect of LLL on the progression of pre-induced AAA.
  
  
  METHODS
  AAA was induced in Apo-E(-/-) mice (age 16-20 weeks) by subcutaneous infusion of angiotensin-II using osmotic minipumps (1000 ng/kg/minutes, 4 weeks). HF-u/s (40 MHz, 0.01 mm resolution, Vevo-770, VisualSonics) was used to measure the maximum cross-sectional-diameter (MCD) of the suprarenal abdominal aorta, the anterior wall displacement (AWD), and radial wall velocity (RWV). The aortas of mice that developed >35% dilatation at 2 weeks over baseline were exposed retroperitoneally and treated with LLL (780 nm, 2.2 J/cm(2), 9 minutes) or sham-operated. HF-u/s was repeated at 4 weeks, the mice sacrificed by perfusion fixation, and the aortas excised for histopathology.
  
  
  RESULTS
  Of all mice with >35% MCD expansion of the suprarenal aorta at 2 weeks, 7(58%) of 12 non-treated, but only 1(7%) of 14 LLL, had increased MCD(> 1 SD) at 4 weeks (P < 0.009 by Fisher's Exact Test [FET]). The mean change in MCD from 2-4 weeks was also markedly reduced in the LLL-treated mice (control vs. LLL, 0.24 ± 0.25 vs. -0.06 ± 0.39 mm, P = 0.029 by unpaired t-test). Similar results were obtained when limiting the analysis to animals with ≥ 50% expansion at 2 weeks. The deterioration in AWD from 2-4 weeks in non-treated controls was not observed in LLL-treated animals (ΔAWD: control, 0.03 ± 0.05 mm, P < 0.036 vs. LLL, 0.00 ± 0.05, P = 0.91 by paired t-test). By the modified Daugherty classification, we found significantly fewer severe aneurysms at 4 weeks in the LLL-treated animals versus control (3 of 10 vs. 9 of 11, P = 0.03 by FET).
  
  
  CONCLUSIONS
  LLL not only prevents de novo development of AAA, but, from this study, also arrests further progression of pre-induced AAA and its associated deterioration in the biomechanical integrity of the aortic wall in Apo-E(-/-) mice.
authors.affiliation: Institute for Medical Research-IMRIC, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Lilach
authors.initials: L
authors.lastname: Gavish
authors.forename: Ronen
authors.initials: R
authors.lastname: Beeri
authors.forename: Dan
authors.initials: D
authors.lastname: Gilon
authors.forename: Chen
authors.initials: C
authors.lastname: Rubinstein
authors.forename: Yacov
authors.initials: Y
authors.lastname: Berlatzky
authors.forename: Atilla
authors.initials: A
authors.lastname: Bulut
authors.forename: Petachia
authors.initials: P
authors.lastname: Reissman
authors.forename: Leah Y
authors.initials: LY
authors.lastname: Gavish
authors.forename: S David
authors.initials: SD
authors.lastname: Gertz
mesh_terms: D000804:Angiotensin II; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000209:etiology / Q000517:prevention & control* / Q000532:radiotherapy*; D001057:Apolipoproteins E / Q000172:deficiency; D004195:Disease Models, Animal; D054023:Lasers, Semiconductor / Q000627:therapeutic use*; D028022:Low-Level Light Therapy; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D001057:Apolipoproteins E; D000804:Angiotensin II
keywords: abdominal aortic aneurysm; aneurysm; angiotensin-II; apolipoprotein-E-deficient mice; low level laser (light) therapy (LLLT); photobiomodulation (PBM)