TY - JOUR
T1 - Pentagalloyl Glucose (PGG) Prevents and Restores Mechanical Changes Caused by Elastic Fiber Fragmentation in the Mouse Ascending Aorta
AU - Crandall, Christie L.
AU - Caballero, Bryant
AU - Viso, Mariana E.
AU - Vyavahare, Naren R.
AU - Wagenseil, Jessica E.
N1 - Publisher Copyright:
© 2022, The Author(s) under exclusive licence to Biomedical Engineering Society.
PY - 2023/4
Y1 - 2023/4
N2 - Thoracic aortic aneurysm (TAA) is characterized by dilation of the aorta that can lead to dissection or rupture. Degradation of elastic fibers is a consistent histopathological feature of TAA that likely contributes to disease progression. Pentagalloyl glucose (PGG) shows promise for stabilizing elastic fibers in abdominal aortic aneurysms, but its efficacy and mechanical effects in the thoracic aorta are unknown. We simulated TAAs using elastase (ELA) to degrade elastic fibers in the mouse ascending aorta and determined the preventative and restorative potential of PGG. Biaxial mechanical tests, constitutive model fitting, and multiphoton imaging were performed on untreated (UNT), PGG, ELA, PGG + ELA, and ELA + PGG treated aortas. PGG treatment alone does not significantly alter mechanical properties or wall structure compared to UNT. ELA treatment alone causes an increase in the unloaded diameter and length, decreased compliance, significant changes in the material constants, and separation of the outer layers of the aortic wall compared to UNT. PGG treatment before or after ELA ameliorates the mechanical and structural changes associated with elastic fiber degradation, with preventative PGG treatment being most effective. These results suggest that PGG is a potential pharmaceutical option to stabilize elastic fibers in TAA.
AB - Thoracic aortic aneurysm (TAA) is characterized by dilation of the aorta that can lead to dissection or rupture. Degradation of elastic fibers is a consistent histopathological feature of TAA that likely contributes to disease progression. Pentagalloyl glucose (PGG) shows promise for stabilizing elastic fibers in abdominal aortic aneurysms, but its efficacy and mechanical effects in the thoracic aorta are unknown. We simulated TAAs using elastase (ELA) to degrade elastic fibers in the mouse ascending aorta and determined the preventative and restorative potential of PGG. Biaxial mechanical tests, constitutive model fitting, and multiphoton imaging were performed on untreated (UNT), PGG, ELA, PGG + ELA, and ELA + PGG treated aortas. PGG treatment alone does not significantly alter mechanical properties or wall structure compared to UNT. ELA treatment alone causes an increase in the unloaded diameter and length, decreased compliance, significant changes in the material constants, and separation of the outer layers of the aortic wall compared to UNT. PGG treatment before or after ELA ameliorates the mechanical and structural changes associated with elastic fiber degradation, with preventative PGG treatment being most effective. These results suggest that PGG is a potential pharmaceutical option to stabilize elastic fibers in TAA.
KW - Biomechanics
KW - Elastase
KW - Elastin
KW - Thoracic aortic aneurysm
UR - http://www.scopus.com/inward/record.url?scp=85139507896&partnerID=8YFLogxK
U2 - 10.1007/s10439-022-03093-x
DO - 10.1007/s10439-022-03093-x
M3 - Article
C2 - 36203118
AN - SCOPUS:85139507896
SN - 0090-6964
VL - 51
SP - 806
EP - 819
JO - Annals of biomedical engineering
JF - Annals of biomedical engineering
IS - 4
ER -