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