Mechanical Stretch Induces Phosphorylation of p38-MAPK and Apoptosis in Human Saphenous Vein

OBJECTIVE: Failure of saphenous vein grafts remains a major limitation of coronary bypass surgery. The aims of the present study were to determine whether pressure distension of human saphenous vein induces the activation of p38-MAPK and to determine its role in apoptosis.

METHODS AND RESULTS: Phosphorylated p38 was detected at basal levels in human saphenous vein obtained immediately after harvesting. Distended saphenous vein showed significantly higher levels of phosphorylated p38 compared with control vein (P<0.01) and nondistended saphenous vein maintained for 3 and 6 hours after harvesting (both P<0.01). Apoptosis in distended and nondistended vein was significantly higher at 24 hours compared with control vein, with distended vein showing increased apoptosis compared with nondistended saphenous vein at all time points investigated (P<0.001). Immunolocalization showed co-localization of phosphorylated p38 and apoptosis. Inhibition of p38 activity reduced the apoptotic index of cultured vascular smooth muscle cells by 72.1%+/-1.2% and cultured distended saphenous vein segments by 72.7%+/-0.9%.

CONCLUSIONS: Pressure distension of intact human saphenous vein induces activation of p38, and this is associated with apoptosis. Inhibition of p38 kinase activity in saphenous vein smooth muscle cells and intact vein reduces apoptosis. These findings contribute to our understanding of the mechanisms of saphenous vein graft failure.