Arrest of progression of pre-induced abdominal aortic aneurysm in apolipoprotein E-deficient mice by low level laser phototherapy

Background and Objectives: 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 preinduced AAA.

Study Design/Material and Methods: AAA was induced in Apo-E^-/- mice (age16-20 weeks) by subcutaneous infusion of angiotensin-II using osmotic minipumps (1000 ng/kg/minutes, 4 weeks). HF-u/s (40 MHz, 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 (780 nm, 2.2 J/cm2, 9 minutes) or sham-operated. HFu/ 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 inMCDfrom 2-4 weeks was also markedly reduced in the LLL-treated mice (control vs. LLL, 0.24±0.25 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 (DAWD: 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).

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.