Increased production of cytokines and growth factors by aortic allografts: A possible explanation for myointimal hyperplasia formation.

Accelerated myointimal hyperplasia is a major complication of arterial allografts. The aim of our study was to analyze the role of growth factors in the genesis of myointimal hyperplasia in arterial allografts. Two groups of experiments were performed: Isografts and Allografts. The Isograft group consisted of 18 inbred Lewis rats in which a 1-cm long segment of aorta was inserted as abdominal aortic interposition graft. The aortic segments were obtained from syngeneic Lewis rats. The Allograft group consisted of 18 inbred Lewis rats, in which a 1-cm long segment of aorta was interposed at the level of the abdominal aorta. The aortic segments were obtained from allogeneic Brown-Norway rats. No immunosuppression was used. The animals were sacrificed 4 weeks after surgery and the aortic grafts were analyzed by light, electron microscopy (n = 3 for each group) and immunohistochemistry (n = 3 for each group). In addition, aortic segments (n = 12 for each group) were put in an organ culture to assess production of growth factors. All allografts showed evidence of severe myointimal hyperplasia, which was minimal in isografts. PDGF, bFGF and TGF-beta(1) production, generally considered to be the cause of myointimal hyperplasia, was not increased in allografts, whereas IL-1, TNF-alpha and GM-CSF production was increased in allografts and probably lymphocytes were the source of these cytokines (p < 0.001). We conclude that myointimal hyperplasia in aortic allografts is associated with an increase of IL-1, TNF-alpha and GM-CSF produced by lymphocytes.

Growth factors and myointimal hyperplasia in experimental aortic allografts.

OBJECTIVES: To analyse the role of growth factors (platelet derived growth factor, PDGF; basic fibroblast growth factor, bFGF; interleukin 1, IL-1) in the genesis of myointimal hyperplasia in arterial allografts. MATERIALS: Two groups of experiments were performed: isografts and allografts. The isograft group consisted of 15 inbred Lewis rats in which a 1 cm long segment of aorta was inserted as an abdominal aortic interposition graft. The aortic segments were obtained from syngenic Lewis rats. The allograft group consisted of 15 inbred Lewis rats, in which a 1 cm long segment of aorta was interposed at the abdominal aorta level. The aortic segments were obtained from allogenic Brown-Norway rats. CHIEF OUTCOME MEASURES: The animals were killed 4 weeks after surgery and were analysed by morphometric analysis (n = 3 for each group). In addition, production of PDGF, bFGF and IL-1 by aortic segments (n = 12 for each group) in organ culture was assessed. MAIN RESULTS: Allografts had more myointimal hyperplasia, than isografts (p < 0.05). PDGF and bFGF production, generally considered to be the cause of myointimal hyperplasia, was not increased in allografts. IL-1 production was higher in allografts (p < 0.001). MAIN CONCLUSIONS: Myointimal hyperplasia in aortic allografts is dependent on growth factors produced by the graft itself. These growth factors are different from PDGF and bFGF that generally have been implicated in the genesis of naturally occurring myointimal hyperplasia and atherosclerosis. IL-1 may have a principal role in the genesis of myointimal hyperplasia in arterial allografts.

Fluid shear stress increases the release of platelet derived growth factor BB (PDGF BB) by aortic endothelial cells.

OBJECTIVES: The aim of this study was to determine the correlation between shear stress and the release of Platelet Derived Growth Factor (PDGF BB) by aortic endothelial cells. DESIGN AND SETTING: Laboratory in vitro study. MATERIALS: Bovine aortic endothelial cells were seeded in fibronectin-coated cylinders at 1.0 x 10(6) cells/tube and allowed to reach confluence and to adhere for 48 hours. The experimental groups were subjected to nonpulsatile, laminar flow of 50, 100, 150 ml/min in polystyrene cylinders (i.d. 10 mm) of a closed circulatory loop giving a shear stress on the endothelial cells of 3, 6, 9 dyn/cm2. The control group was subjected to similar incubation conditions without flow. OUTCOME MEASURES: The release of PDGF BB by endothelial cells was measured by ELISA and Western Blot Analysis. RESULTS: Shear stress increased significantly (p < 0.01) the release of PDGF BB by endothelial cells. CONCLUSIONS: PDGF BB release by endothelial cells may be one of the mechanisms linking hemodynamic forces and adaptation of blood vessels wall.