TY - JOUR
T1 - Asymmetric Cell–Matrix and Biomechanical Abnormalities in Elastin Insufficiency Induced Aortopathy
AU - Krishnamurthy, Varun K.
AU - Evans, Ashlie N.
AU - Wansapura, Janaka P.
AU - Osinska, Hanna
AU - Maddy, Kelsey E.
AU - Biechler, Stefanie V.
AU - Narmoneva, Daria A.
AU - Goodwin, Richard L.
AU - Hinton, Robert B.
N1 - Publisher Copyright:
© 2014, Biomedical Engineering Society.
PY - 2014/10
Y1 - 2014/10
N2 - Aortopathy is characterized by vascular smooth muscle cell (VSMC) abnormalities and elastic fiber fragmentation. Elastin insufficient (Eln+/−) mice demonstrate latent aortopathy similar to human disease. We hypothesized that aortopathy manifests primarily in the aorto-pulmonary septal (APS) side of the thoracic aorta due to asymmetric cardiac neural crest (CNC) distribution. Anatomic (aortic root vs. ascending aorta) and molecular (APS vs. non-APS) regions of proximal aorta tissue were examined in adult and aged wild type (WT) and mutant (Eln+/−) mice. CNC, VSMCs, elastic fiber architecture, proteoglycan expression, morphometrics and biomechanical properties were examined using histology, 3D reconstruction, micropipette aspiration and in vivo magnetic resonance imaging (MRI). In the APS side of Eln+/− aorta, Sonic Hedgehog (SHH) is decreased while SM22 is increased. Elastic fiber architecture abnormalities are present in the Eln+/− aortic root and APS ascending aorta, and biglycan is increased in the aortic root while aggrecan is increased in the APS aorta. The Eln+/− ascending aorta is stiffer than the aortic root, the APS side is thicker and stiffer than the non-APS side, and significant differences in the individual aortic root sinuses are observed. Asymmetric structure–function abnormalities implicate regional CNC dysregulation in the development and progression of aortopathy.
AB - Aortopathy is characterized by vascular smooth muscle cell (VSMC) abnormalities and elastic fiber fragmentation. Elastin insufficient (Eln+/−) mice demonstrate latent aortopathy similar to human disease. We hypothesized that aortopathy manifests primarily in the aorto-pulmonary septal (APS) side of the thoracic aorta due to asymmetric cardiac neural crest (CNC) distribution. Anatomic (aortic root vs. ascending aorta) and molecular (APS vs. non-APS) regions of proximal aorta tissue were examined in adult and aged wild type (WT) and mutant (Eln+/−) mice. CNC, VSMCs, elastic fiber architecture, proteoglycan expression, morphometrics and biomechanical properties were examined using histology, 3D reconstruction, micropipette aspiration and in vivo magnetic resonance imaging (MRI). In the APS side of Eln+/− aorta, Sonic Hedgehog (SHH) is decreased while SM22 is increased. Elastic fiber architecture abnormalities are present in the Eln+/− aortic root and APS ascending aorta, and biglycan is increased in the aortic root while aggrecan is increased in the APS aorta. The Eln+/− ascending aorta is stiffer than the aortic root, the APS side is thicker and stiffer than the non-APS side, and significant differences in the individual aortic root sinuses are observed. Asymmetric structure–function abnormalities implicate regional CNC dysregulation in the development and progression of aortopathy.
KW - Aortic root
KW - Biomedical engineering
KW - Cardiac neural crest
KW - Elastic fibers
KW - Micropipette aspiration
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U2 - 10.1007/s10439-014-1072-y
DO - 10.1007/s10439-014-1072-y
M3 - Article
C2 - 25099772
AN - SCOPUS:84920255163
SN - 0090-6964
VL - 42
SP - 2014
EP - 2028
JO - Annals of biomedical engineering
JF - Annals of biomedical engineering
IS - 10
ER -