Measuring, reversing, and modeling the mechanical changes due to the absence of Fibulin-4 in mouse arteries

Victoria P. Le, Yoshito Yamashiro, Hiromi Yanagisawa, Jessica E. Wagenseil

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1081-1095
Number of pages15
JournalBiomechanics and Modeling in Mechanobiology
Volume13
Issue number5
DOIs
StatePublished - 2014

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Aneurysm
Aorta
Arteries
Mouse
Muscle
Genes
Cells
Modeling
Angiotensin II
Smooth muscle Cells
Compliance
Smooth Muscle Myocytes
Pathophysiology
Gene
Biological Models
Remodeling
Aortic Aneurysm
Mechanical Behavior
fibulin-4
Dilation

Keywords

  • Constrained mixture model
  • Extracellular matrix
  • Vascular mechanics

ASJC Scopus subject areas

  • Biotechnology
  • Mechanical Engineering
  • Modeling and Simulation

Cite this

Measuring, reversing, and modeling the mechanical changes due to the absence of Fibulin-4 in mouse arteries. / Le, Victoria P.; Yamashiro, Yoshito; Yanagisawa, Hiromi; Wagenseil, Jessica E.

In: Biomechanics and Modeling in Mechanobiology, Vol. 13, No. 5, 2014, p. 1081-1095.

Research output: Contribution to journalArticle

Le, Victoria P. ; Yamashiro, Yoshito ; Yanagisawa, Hiromi ; Wagenseil, Jessica E. / Measuring, reversing, and modeling the mechanical changes due to the absence of Fibulin-4 in mouse arteries. In: Biomechanics and Modeling in Mechanobiology. 2014 ; Vol. 13, No. 5. pp. 1081-1095.
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