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

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Background and ObjectivesUsing non‐invasive, high‐frequency ultrasonography (HF‐u/s), we showed that low‐level laser phototherapy (LLL) inhibitsde‐novoformation of abdominal aortic aneurysms (AAA) in apolipoprotein‐E‐deficient (Apo‐E‐/‐) mice. The current study tests the effect of LLL on the progression ofpre‐inducedAAA.Study Design/Material and MethodsAAA 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, 0.01 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/cm2, 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.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(> 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 ± 0.39mm,P = 0.029 by unpairedt‐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 pairedt‐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 preventsde novodevelopment of AAA, but, from this study, also arrests further progression ofpre‐inducedAAA and its associated deterioration in the biomechanical integrity of the aortic wall in Apo‐E‐/‐mice. Lasers Surg. Med. 46:781–790, 2014. © 2014 Wiley Periodicals, Inc.
Title: Arrest of progression of pre‐induced abdominal aortic aneurysm in apolipoprotein E‐deficient mice by low level laser phototherapy
Description:
Background and ObjectivesUsing non‐invasive, high‐frequency ultrasonography (HF‐u/s), we showed that low‐level laser phototherapy (LLL) inhibitsde‐novoformation of abdominal aortic aneurysms (AAA) in apolipoprotein‐E‐deficient (Apo‐E‐/‐) mice.
The current study tests the effect of LLL on the progression ofpre‐inducedAAA.
Study Design/Material and MethodsAAA 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.
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/cm2, 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.
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(> 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.
39mm,P = 0.
029 by unpairedt‐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 pairedt‐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 preventsde novodevelopment of AAA, but, from this study, also arrests further progression ofpre‐inducedAAA and its associated deterioration in the biomechanical integrity of the aortic wall in Apo‐E‐/‐mice.
Lasers Surg.
Med.
46:781–790, 2014.
© 2014 Wiley Periodicals, Inc.

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