epidermal-growth-factor and Peripheral-Vascular-Diseases

About a quarter of peripheral vein grafts fail due in part to intimal hyperplasia. The proliferative capacity and response to growth inhibitors of medial smooth muscle cells and adventitial fibroblasts in vitro were studied to test the hypothesis that intrinsic differences in cells of vein grafts are associated with graft failure.. Cells were grown from explants of the medial and adventitial layers of samples of vein grafts obtained at the time of implantation. Vein graft patency and function were monitored over the first 12 months using ankle pressures and Duplex ultrasound to determine vein graft status. Cells were obtained from veins from 11 patients whose grafts remained patent (non-stenotic) and from seven patients whose grafts developed stenosis. Smooth muscle cells (SMCs) derived from media and fibroblasts derived from adventitia were growth arrested in serum-free medium and then stimulated with 1 muM sphingosine-1-phosphate (S1P), 10 nM thrombin, 10 ng/ml epidermal growth factor (EGF), 10 ng/ml platelet-derived growth factor-BB (PDGF-BB), PDGF-BB plus S1P, or PDGF-BB plus thrombin for determination of incorporation of [(3)H]-thymidine into DNA. Cells receiving PDGF-BB or thrombin were also treated with or without 100 microg/ml heparin, which is a growth inhibitor. Cells receiving thrombin were also treated with or without 150 nM AG1478, an EGF receptor kinase inhibitor.. SMCs and fibroblasts from veins of patients that developed stenosis responded more to the growth factors, such as PDGF-BB alone or in combination with thrombin or S1P, than cells from veins of patients that remained patent (P = .012). In addition, while PDGF-BB-mediated proliferation of fibroblasts from grafts that remained patent was inhibited by heparin (P < .03), PDGF-BB-mediated proliferation of fibroblasts from veins that developed stenosis was not (P > .5).. Inherent differences in the proliferative response of vein graft cells to PDGF-BB and heparin may explain, in part, the variability among patients regarding long term patency of vein grafts.

Topics: Aged; Ankle; Becaplermin; Blood Pressure; Cell Proliferation; Cells, Cultured; Constriction, Pathologic; DNA Replication; Epidermal Growth Factor; Female; Fibroblasts; Graft Occlusion, Vascular; Heparin; Humans; Hyperplasia; Lower Extremity; Lysophospholipids; Male; Middle Aged; Myocytes, Smooth Muscle; Peripheral Vascular Diseases; Platelet-Derived Growth Factor; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-sis; Quinazolines; Saphenous Vein; Sphingosine; Thrombin; Time Factors; Tyrphostins; Ultrasonography, Doppler, Duplex; Vascular Patency

Bone marrow mononuclear cell (BM-MNC) implantation (BMI) for critical severe limb ischemia especially for Buerger's disease shows excellent clinical results but the mechanism of this treatment is still unknown. In this study, we investigated the changes in serum levels of angiogenesis-related factors after BMI treatment.. Twelve patients whose BMI treatments were clinically very effective was selected out of ninteen cases, nine patients had Buerger's disease, two patients had arteriosclerosis obliterans and one had systemic sclerosis. Venous bood from femoral vein or brachial vein of the recipient limbs of these patients.. Adrenomedulin (AM), soluble vascular cell adhesion molecule-1 (sVCAM-1), and C-reactive protein (CRP) serum levels 24 h after BMI treatment were significantly increased compared with those before BMI treatment (p < 0.05). Vascular endothelial growth factor (VEGF) serum levels after BMI treatment significantly increased between 1 week and 3 months after BMI treatment (p < 0.05). Nitric oxide (NO) serum levels after BMI treatment increased significantly 2 weeks after BMI treatment (p < 0.05). There was no correlation between the numbers of implanted cells and serum levels of measured angiogenesis-related factors that were significantly increased after BMI treatment.. It was concluded that the mechanism underlying BMI treatment consists of early and late phases. The early phase involves the direct action by implanted cells, and the late phase involves indirect paracrine action. In addition, it was considered that BMI treatment is effective when we implant a sufficient level of bone marrow (600 ml) to treat severe limb ischemia.

Topics: Adrenomedullin; Adult; Aged; Arterial Occlusive Diseases; C-Reactive Protein; Convalescence; Epidermal Growth Factor; Female; Fibroblast Growth Factor 2; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Hepatocyte Growth Factor; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-1beta; Ischemia; Leg; Male; Middle Aged; Nitric Oxide; Peripheral Vascular Diseases; Postoperative Period; Transplantation, Autologous; Vascular Cell Adhesion Molecule-1; Vascular Endothelial Growth Factor A