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Annals of Biomedical Engineering

, Volume 42, Issue 10, pp 2014–2028 | Cite as

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

  • Varun K. Krishnamurthy
  • Ashlie N. Evans
  • Janaka P. Wansapura
  • Hanna Osinska
  • Kelsey E. Maddy
  • Stefanie V. Biechler
  • Daria A. Narmoneva
  • Richard L. Goodwin
  • Robert B. HintonEmail author
Article

Abstract

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.

Keywords

Aortic root Cardiac neural crest Elastic fibers Micropipette aspiration Biomedical engineering 

Abbreviations

APS

Aorto-pulmonary septum

CNC

Cardiac neural crest

ECM

Extracellular matrix

EFF

Elastic fiber fragmentation

Eln/

Homozygous deletion of elastin gene

Eln+/−

Heterozygous deletion of elastin gene

IOD

Integrated optical density

MRI

Magnetic resonance imaging

MRSD

Maximum rate of systolic distension

PTA

Persistent truncus arteriosus

SHH

Sonic hedgehog

TAA

Thoracic aortic aneurysm

VSMC

Vascular smooth muscle cell

WT

Wild type

Notes

Acknowledgments

We thank Amy Opoka for her assistance. We also thank Dr. Dean Y. Li (University of Utah) for providing the elastin knockout mice and Dr. Robert P. Mecham (Washington University) for helpful discussions. Present address for Varun K. Krishnamurthy: Department of Bioengineering, Rice University, Houston, TX 77005, USA. This work was supported by the AHA 11PRE7210044 (VKK), NIH HL086856-01 (RLG), NIH HL085122 (RBH), and Cincinnati Children’s Research Foundation (RBH).

Disclosures

The authors have nothing to disclose.

Supplementary material

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Copyright information

© Biomedical Engineering Society 2014

Authors and Affiliations

  • Varun K. Krishnamurthy
    • 1
    • 2
  • Ashlie N. Evans
    • 3
  • Janaka P. Wansapura
    • 4
  • Hanna Osinska
    • 5
  • Kelsey E. Maddy
    • 6
  • Stefanie V. Biechler
    • 6
  • Daria A. Narmoneva
    • 2
  • Richard L. Goodwin
    • 3
  • Robert B. Hinton
    • 1
    Email author
  1. 1.Division of Cardiology, the Heart InstituteCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  2. 2.Department of Biomedical EngineeringUniversity of CincinnatiCincinnatiUSA
  3. 3.Department of Biomedical EngineeringUniversity of South CarolinaColumbiaUSA
  4. 4.Division of RadiologyCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  5. 5.Division of Molecular Cardiovascular BiologyCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  6. 6.Department of Cell Biology and AnatomyUniversity of South CarolinaColumbiaUSA

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