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 investigate 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 approximately 140 times immediately after surgery compared with that in the venous wall. This change was associated with an increase in the percentage of TUNEL-positive cells at 1, 6, 24, 120, 240, and 720h with two distinct peaks at 1 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 24h, respectively). When tensile stress and strain in the vein graft wall were reduced 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 24h, respectively). Furthermore, DEVD-CHO, a tetrapeptide aldehyde that inhibits the activity of caspase 3, significantly suppressed this event. These results suggest 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.
Moore
M M
MM
Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208-3107, USA.
Goldman
J
J
Patel
A R
AR
Chien
S
S
Liu
S Q
SQ
D000714:Anastomosis, Surgical; D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects; D016923:Cell Death / Q000502:physiology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000473:pathology* / Q000503:physiopathology; D007601:Jugular Veins / Q000601:surgery*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D013718:Tensile Strength / Q000502:physiology*
D015853:Cysteine Proteinase Inhibitors; D009842:Oligopeptides; C108637:aspartyl-glutamyl-valyl-aspartal; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases