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Updated: Oct 31, 2025
Human Saphenous Vein Endothelial Cell Isolation and Exposure to Controlled Levels of Shear Stress and Stretch
Published on: April 21, 2023
High stretch induces endothelial dysfunction accompanied by oxidative stress and actin remodeling in human saphenous
T Girão-Silva1, M H Fonseca-Alaniz1, J C Ribeiro-Silva1
1Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, Av. Dr. Eneas de Carvalho Aguiar, 44-Bloco II, 10 Andar, São Paulo, SP, 05403-000, Brazil.
Insights
High stretch damages vein cells used in bypass surgery by increasing oxidative stress and altering cell structure. This dysfunction in saphenous vein endothelial cells (hSVECs) may lead to graft failure after coronary artery bypass graft (CABG) surgery.
Area of Science:
- Vascular biology
- Endothelial cell biology
- Biomedical engineering
Background:
- Coronary artery bypass graft (CABG) surgery outcomes are limited by saphenous vein graft remodeling.
- Endothelial dysfunction is a potential contributor to saphenous vein graft failure.
- High mechanical stretch (HS) is a factor experienced by vein grafts in vivo.
Purpose of the Study:
- To investigate if high stretch (HS) induces dysfunction in human saphenous vein endothelial cells (hSVECs).
- To identify the underlying molecular mechanisms of HS-induced hSVEC dysfunction.
Main Methods:
- In vitro experiments exposing hSVECs to HS conditions.
- Measurement of nitric oxide (NO) bioavailability.
- Assessment of inflammatory adhesion molecule expression (E-selectin, VCAM1).
- Analysis of actin cytoskeleton dynamics (F-actin, G-actin, cofilin).
- Quantification of reactive oxidative species (ROS) production.
- Evaluation of the effects of N-acetylcysteine (NAC) as an antioxidant.
Main Results:
- HS reduced NO bioavailability in hSVECs.
- HS increased E-selectin and VCAM1 expression, enhancing THP-1 cell adhesion.
- HS led to decreased F-actin and altered G-actin/cofilin localization in hSVECs.
- HS elevated ROS levels in hSVECs.
- NAC pre-treatment mitigated HS-induced changes in actin remodeling and inflammatory markers.
Conclusions:
- High stretch induces human saphenous vein endothelial cell dysfunction.
- Increased oxidative stress and actin cytoskeleton remodeling are key mechanisms in HS-induced hSVEC dysfunction.
- These findings suggest a role for HS-induced endothelial dysfunction in saphenous vein graft failure after CABG.
Abstract:
The rate of the remodeling of the arterialized saphenous vein conduit limits the outcomes of coronary artery bypass graft surgery (CABG), which may be influenced by endothelial dysfunction. We tested the hypothesis that high stretch (HS) induces human saphenous vein endothelial cell (hSVEC) dysfunction and examined candidate underlying mechanisms. Our results showed that in vitro HS reduces NO bioavailability, increases inflammatory adhesion molecule expression (E-selectin and VCAM1) and THP-1 cell adhesion. HS decreases F-actin in hSVECs, but not in human arterial endothelial cells, and is accompanied by G-actin and cofilin's nuclear shuttling and increased reactive oxidative species (ROS). Pre-treatment with the broad-acting antioxidant N-acetylcysteine (NAC) supported this observation and diminished stretch-induced actin remodeling and inflammatory adhesive molecule expression. Altogether, we provide evidence that increased oxidative stress and actin cytoskeleton remodeling play a role in HS-induced saphenous vein endothelial cell dysfunction, which may contribute to predisposing saphenous vein graft to failure.
