Intimal thickening involves transdifferentiation of embryonic endothelial cells

Area of Science:

• Vascular Biology
• Developmental Biology
• Cell Biology

Background:

• The origin of vascular smooth muscle cells (SMCs) has been debated, with a recent hypothesis suggesting endothelial cell origins.
• Understanding the mechanisms of endothelial-to-smooth muscle cell transdifferentiation is crucial for vascular development research.

Purpose of the Study:

• To investigate the in vivo phenotype of cells in the aortic wall of chicken embryos.
• To determine if intimal thickening cells originate from endothelial cell transdifferentiation.
• To explore the role of TGFbeta-3 in endothelial-to-mesenchymal transition.

Main Methods:

• Immunolabeling of serial cryosections of chicken embryo aortas.
• Culture and observation of aortic explants from 14-day-old chicken embryos.
• Analysis of vWf and smooth muscle alpha-actin (SM alpha-actin) expression.
• Immunoreactivity assessment for TGFbeta-3.

Main Results:

• Mesenchymal cells in the intimal thickening showed potential endothelial origins.
• Explanted endothelial cells exhibited loss of cobblestone morphology, migration, and some acquired SM alpha-actin expression.
• Transitional cells were identified, losing vWf and gaining SM alpha-actin.
• TGFbeta-3 immunoreactivity was associated with migrating mesenchymal cells and decreased with differentiation.

Conclusions:

• Embryonic aortic endothelial cells can transdifferentiate into mesenchymal cells, some expressing SM alpha-actin.
• Findings support the origin of certain vascular cells from endothelium, explaining fetal-like cells and intimal thickening.
• TGFbeta-3 may play a role in endothelial-to-mesenchymal transition during aortic development.