Asymmetric Cell–Matrix and Biomechanical Abnormalities in Elastin Insufficiency Induced Aortopathy

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...

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Bibliographic Details
Published in:Annals of biomedical engineering 2014-10, Vol.42 (10), p.2014-2028
Main Authors: Krishnamurthy, Varun K., Evans, Ashlie N., Wansapura, Janaka P., Osinska, Hanna, Maddy, Kelsey E., Biechler, Stefanie V., Narmoneva, Daria A., Goodwin, Richard L., Hinton, Robert B.
Format: Article
Language:English
Subjects:
Aging - physiology
Animals
Aorta - abnormalities
Aorta - physiology
Aortic Diseases - pathology
Aortic Diseases - physiopathology
Biochemistry
Biological and Medical Physics
Biomechanical Phenomena
Biomedical and Life Sciences
Biomedical Engineering and Bioengineering
Biomedicine
Biophysics
Child
Classical Mechanics
Elastic Modulus
Elastin - deficiency
Elastin - genetics
Elastin - physiology
Humans
Mice, Transgenic
Myocytes, Smooth Muscle - pathology
Neural Crest - abnormalities
Proteoglycans - metabolism
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Summary: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.
ISSN:0090-6964
1573-9686
DOI:10.1007/s10439-014-1072-y