Modulation of mechanosensitive genes during embryonic aortic arch development.

Area of Science:

• Developmental biology
• Cardiovascular research
• Vascular development

Background:

• Embryonic aortic arches (AA) are dynamic vascular structures crucial for forming the great arteries.
• A prior study mapped mechanosensitive gene expression in AA under altered mechanical loads in avian embryos.

Purpose of the Study:

• To validate a mechanosensitive gene expression map of embryonic aortic arches.
• To investigate the effects of perturbing key genes on vascular microstructure and material properties.

Main Methods:

• Utilized an in-house microvascular gene knockdown system in avian embryos.
• Performed in vivo measurements, confirmed by immunohistochemistry, western blotting, and computational modeling of the vascular extracellular matrix (ECM).

Main Results:

• TGFβ3 knockdown reduced expression of TGFβ3 and downstream targets (ELN, Fbn1, COL1, COL3), increasing left AA diameter by 23%.
• MMP2 knockdown decreased MMP2 expression, increased COL3 by 6-fold, reduced AA wall stiffness, and increased AA diameter by 55%.
• siRNA vectors effectively decreased target gene expression without significant inter-vector differences.

Conclusions:

• Spatial genetic modification in the embryonic aortic arch region dictates vascular phenotype and ECM composition.
• Findings can be integrated with models of mechanically-induced congenital heart disease.