Role of tensile stress and strain in the induction of cell death in experimental vein grafts

Tensile stress and strain are known to induce vascular cell proliferation, a process that is physiologically counterbalanced by cell death. Here we in vestigate whether tensile stress and strain regulate vascular-cell death by using an end-to-end anastomosed rat vein graft model. In such a model, the circumferential tensile stress in the graft wall was increased by similar to 140 times immediately after surgery compared with that in the venous wal l. This change was associated with an increase in the percentage of TUNEL-p ositive cells at 1, 6, 24, 120, 240, and 720 h with two distinct peaks at I and 24h (10.1 +/- 3.5 and 14.4 +/- 3.2%, respectively) compared with that in control jugular veins (0.4 +/- 0.5 and 0.5 +/- 0.5% at 1 and 24 h, respe ctively). When tensile stress and strain in the vein graft wall were reduce d by using a biomechanical engineering approach, the rate of cell death was reduced significantly (3.6 +/- 1.1 and 1.6 +/- 0.5% at 1 and 24 h, respect ively). Furthermore, DEVD-CHO, a tetrapeptide aldehyde that inhibits the ac tivity of caspase 3, significantly suppressed this event. These results sug gest that a step increase in tensile stress and strain in experimental vein grafts induces rapid cell death, which is possibly mediated by cell death signaling mechanisms. (C) 2001 Elsevier Science Ltd. All rights reserved.