Increased blood flow induces regression of intimal hyperplasia.
We have previously shown that high shear stress inhibits growth of developing neointima in a primate model of polytetrafluoroethylene (PTFE) graft healing. We used this model to test the hypothesis that increased shear stress can cause atrophy of an established neointima. High porosity PTFE grafts were inserted into the aorto-iliac circulation bilaterally in baboons. These grafts develop neointimal hyperplasia comprising smooth muscle cells and a luminal surface of confluent endothelium. Neointima was allowed to develop for 2 months. At that time 8 animals were sacrificed. In eight other animals blood flow in one of two grafts was increased by construction of a femoral arterio-venous fistula. These animals were sacrificed 2 months later (4 months after graft placement). At four months, intimal cross sectional area was smaller on the high shear stress side compared to the contralateral, normal shear stress side (2.53 +/- 0.75 versus 6.83 +/- 0.65 mm2, P < .05). Neointima from grafts exposed to 2 months normal shear stress followed by 2 months of high shear stress had regressed when compared to normal-shear stress grafts studied at 2 months (2.53 +/- 0.75 versus 4.56 +/- 0.68 mm2, P < .05). Morphometric analysis using transmission electron microscopy revealed that the decrease in intimal cross sectional area was attributable to a loss of both smooth muscle cells and matrix. Endothelial nitric oxide synthase was induced in high-flow graft intima. These observations support the conclusion that elevated shear stress can cause vessel wall atrophy. This process might be mediated by nitric oxide.
Mattsson
E J
EJ
Department of Surgery, University of Washington School of Medicine, Seattle 98195-6410, USA.
Kohler
T R
TR
Vergel
S M
SM
Clowes
A W
AW
D000818:Animals; D001807:Blood Vessel Prosthesis; D006965:Hyperplasia; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010215:Papio; D011138:Polytetrafluoroethylene; D012039:Regional Blood Flow; D013314:Stress, Mechanical; D017539:Tunica Intima / Q000473:pathology*
D009569:Nitric Oxide; D011138:Polytetrafluoroethylene; D019001:Nitric Oxide Synthase