Mechanical Strain Induces Transcriptomic Reprogramming of Saphenous Vein Progenitors

Area of Science:

• Vascular Biology
• Cellular and Molecular Medicine
• Biomedical Engineering

Background:

• Intimal hyperplasia causes saphenous vein graft failure after coronary artery bypass surgery.
• The impact of mechanical stress on saphenous vein progenitors (SVPs) is not well understood.
• SVPs reside in the adventitia and possess differentiation potential.

Purpose of the Study:

• To investigate the effects of mechanical strain on SVPs.
• To identify molecular changes in SVPs under cyclic strain.
• To explore the role of AMIGO2 in SVP response to mechanical stress.

Main Methods:

• Global transcriptomic profiling of SVPs under uniaxial cyclic strain in vitro.
• Quantitative analysis of AMIGO2 expression in strained SVPs.
• In vivo validation using a porcine saphenous vein arterialization model.

Main Results:

• Cyclic strain induced stretch-dependent gene regulation in SVPs.
• Adhesion Molecule with Ig Like Domain 2 (AMIGO2) was significantly overexpressed in strained SVPs.
• AMIGO2 upregulation correlated with TGF-β pathway activation and altered cell interactions.
• AMIGO2 expression was confirmed in vivo in an arterialized environment.

Conclusions:

• Mechanical stress induces phenotypic switching in SVPs.
• Increased AMIGO2 expression by SVPs contributes to altered cellular responses.
• Targeting AMIGO2 may improve outcomes for saphenous vein bypass grafts.