Microstructure of early embryonic aortic arch and its reversibility following mechanically altered hemodynamic load release

Merve Celik, Selda Goktas, Cansu Karakaya, Ayse Idil Cakiroglu, Sercin Karahuseyinoglu, S Samaneh Lashkarinia, Erhan Ermek, Kerem Pekkan (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Scopus)


In the embryonic heart, blood flow is distributed through a bilaterally paired artery system composed of the aortic arches (AAs). The purpose of this study is to establish an understanding of the governing mechanism of microstructural maturation of the AA matrix and its reversibility, toward the desired macroscopic vessel lumen diameter and thickness for healthy, abnormal, and in ovo repaired abnormal mechanical loading. While matrix-remodeling mechanisms were significantly different for normal versus conotruncal banding (CTB), both led to an increase in vessel lumen. Correlated with right-sided flow increase at Hamburger & Hamilton stages 21, intermittent load switching between collagen I and III with elastin and collagen-IV defines the normal process. However, decreases in collagen I, elastin, vascular endothelial growth factor-A, and fibrillin-1 in CTB were recovered almost fully following the CTB-release model, primarily because of the pressure load changes. The complex temporal changes in matrix proteins are illustrated through a predictive finite-element model based on elastin and collagen load-sharing mechanism to achieve lumen area increase and thickness increase resulting from wall shear stress and tissue strain, respectively. The effect of embryonic timing in cardiac interventions on AA microstructure was established where abnormal mechanical loading was selectively restored at the key stage of development. Recovery of the normal mechanical loading via early fetal intervention resulted in delayed microstructural maturation. Temporal elastin increase, correlated with wall shear stress, is required for continuous lumen area growth.NEW & NOTEWORTHY The present study undertakes comparative analyses of the mechanistic differences of the arterial matrix microstructure and dynamics in the three fundamental processes of control, conotruncal banded, and released conotruncal band in avian embryo. Among other findings, this study provides specific evidence on the restorative role of elastin during the early lumen growth process. During vascular development, a novel intermittent load-switching mechanism between elastin and collagen, triggered by a step increase in wall shear stress, governs the chronic vessel lumen cross-sectional area increase. Mimicking the fetal cardiovascular interventions currently performed in humans, the early release of the abnormal mechanical load rescues the arterial microstructure with time lag.

Original languageEnglish
Pages (from-to)H1208-H1218
JournalAmerican Journal of Physiology : Heart and Circulatory Physiology
Issue number5
Publication statusPublished - 1 May 2020
Externally publishedYes


  • Animals
  • Aorta, Thoracic/embryology
  • Chick Embryo
  • Collagen/metabolism
  • Coronary Circulation
  • Elastin/metabolism
  • Hemodynamics
  • Stress, Mechanical
  • Vascular Endothelial Growth Factor A/metabolism


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