Mechanical Strain Induces Transcriptomic Reprogramming of Saphenous Vein Progenitors

The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm. nih.gov/, GSE192712

Intimal hyperplasia is the leading cause of graft failure in aortocoronary bypass grafts
performed using human saphenous vein (SV). The long-termconsequences of the altered
pulsatile stress on the cells that populate the vein wall remains elusive, particularly
the effects on saphenous vein progenitors (SVPs), cells resident in the vein adventitia
with a relatively wide differentiation capacity. In the present study, we performed global
transcriptomic profiling of SVPs undergoing uniaxial cyclic strain in vitro. This type of
mechanical stimulation is indeed involved in the pathology of the SV. Results showed
a consistent stretch-dependent gene regulation in cyclically strained SVPs vs. controls,
especially at 72 h. We also observed a robust mechanically related overexpression of
Adhesion Molecule with Ig Like Domain 2 (AMIGO2), a cell surface type I transmembrane
protein involved in cell adhesion. The overexpression of AMIGO2 in stretched SVPs
was associated with the activation of the transforming growth factor b pathway and
modulation of intercellular signaling, cell-cell, and cell-matrix interactions. Moreover,
the increased number of cells expressing AMIGO2 detected in porcine SV adventitia
using an in vivo arterialization model confirms the upregulation of AMIGO2 protein
by the arterial-like environment. These results show that mechanical stress promotes
SVPs’molecular phenotypic switching and increases their responsiveness to extracellular
environment alterations, thus prompting the targeting of new molecular effectors to
improve the outcome of bypass graft procedure.