TY - JOUR
T1 - Measuring, reversing, and modeling the mechanical changes due to the absence of Fibulin-4 in mouse arteries
AU - Le, Victoria P.
AU - Yamashiro, Yoshito
AU - Yanagisawa, Hiromi
AU - Wagenseil, Jessica E.
N1 - Publisher Copyright:
© 2014, Springer-Verlag Berlin Heidelberg.
PY - 2014/10
Y1 - 2014/10
N2 - Mice with a smooth muscle cell (SMC)-specific deletion of Fibulin-4 (SMKO) show decreased expression of SMC contractile genes, decreased circumferential compliance, and develop aneurysms in the ascending aorta. Neonatal administration of drugs that inhibit the angiotensin II pathway encourages the expression of contractile genes and prevents aneurysm development, but does not increase compliance in SMKO aorta. We hypothesized that multidimensional mechanical changes in the aorta and/or other elastic arteries may contribute to aneurysm pathophysiology. We found that the SMKO ascending aorta and carotid artery showed mechanical changes in the axial direction. These changes were not reversed by angiotensin II inhibitors, hence reversing the axial changes is not required for aneurysm prevention. Mechanical changes in the circumferential direction were specific to the ascending aorta; therefore, mechanical changes in the carotid do not contribute to aortic aneurysm development. We also hypothesized that a published model of postnatal aortic growth and remodeling could be used to investigate mechanisms behind the changes in SMKO aorta and aneurysm development over time. Dimensions and mechanical behavior of adult SMKO aorta were reproduced by the model after modifying the initial component material constants and the aortic dilation with each postnatal time step. The model links biological observations to specific mechanical responses in aneurysm development and treatment.
AB - Mice with a smooth muscle cell (SMC)-specific deletion of Fibulin-4 (SMKO) show decreased expression of SMC contractile genes, decreased circumferential compliance, and develop aneurysms in the ascending aorta. Neonatal administration of drugs that inhibit the angiotensin II pathway encourages the expression of contractile genes and prevents aneurysm development, but does not increase compliance in SMKO aorta. We hypothesized that multidimensional mechanical changes in the aorta and/or other elastic arteries may contribute to aneurysm pathophysiology. We found that the SMKO ascending aorta and carotid artery showed mechanical changes in the axial direction. These changes were not reversed by angiotensin II inhibitors, hence reversing the axial changes is not required for aneurysm prevention. Mechanical changes in the circumferential direction were specific to the ascending aorta; therefore, mechanical changes in the carotid do not contribute to aortic aneurysm development. We also hypothesized that a published model of postnatal aortic growth and remodeling could be used to investigate mechanisms behind the changes in SMKO aorta and aneurysm development over time. Dimensions and mechanical behavior of adult SMKO aorta were reproduced by the model after modifying the initial component material constants and the aortic dilation with each postnatal time step. The model links biological observations to specific mechanical responses in aneurysm development and treatment.
KW - Constrained mixture model
KW - Extracellular matrix
KW - Vascular mechanics
UR - http://www.scopus.com/inward/record.url?scp=84920257325&partnerID=8YFLogxK
U2 - 10.1007/s10237-014-0556-x
DO - 10.1007/s10237-014-0556-x
M3 - Article
C2 - 24526456
AN - SCOPUS:84920257325
SN - 1617-7959
VL - 13
SP - 1081
EP - 1095
JO - Biomechanics and Modeling in Mechanobiology
JF - Biomechanics and Modeling in Mechanobiology
IS - 5
ER -