Arrest of Progression of Pre-Induced Abdominal Aortic Aneurysm in Apolipoprotein E-Deficient Mice by Low Level Laser Phototherapy

Background and ObjectivesUsing 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. Study Design/Material and MethodsAAA was induced in Apo-E-/- mice (age16-20 weeks) by subcutaneous infusion of angiotensin-II using osmotic minipumps (1000ng/kg/minutes, 4 weeks). HF-u/s (40MHz, 0.01mm 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 (780nm, 2.2J/cm(2), 9minutes) or sham-operated. HF-u/s was repeated at 4 weeks, the mice sacrificed by perfusion fixation, and the aortas excised for histopathology. ResultsOf 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(>1SD) at 4weeks (P<0.009 by Fisher's Exact Test [FET]). The mean change in MCD from 2-4weeks was also markedly reduced in the LLL-treated mice (control vs. LLL, 0.240.25 vs. -0.06 +/- 0.39mm, 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 (AWD: control, 0.03 +/- 0.05mm, 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). ConclusionsLLL 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. Lasers Surg. Med. 46:781-790, 2014. (c) 2014 Wiley Periodicals, Inc.