The effect of locally administered anti-growth factor antibodies on neointimal hyperplasia formation in expanded polytetrafluoroethylene grafts.
The selective blockage of platelet-derived growth factor BB (PDGF-BB), basic fibroblast growth factor (bFGF), and transforming growth factor beta1 (TGF-beta1) by specific antibodies coated into expanded polytetrafluoroethylene (ePTFE) grafts may diminish neointimal hyperplasia. Sixty pigs were divided into two groups (n = 30 each) and then further divided into five subgroups. Group 1 had a bilateral iliac artery ePTFE interposition graft precoated with Matrigel. Three subgroups (A, B, and C) received a specific monoclonal antibody against PDGF-BB, bFGF, or TGF-beta1. One (D) received all antibodies, and one served as control (nonimmune immunoglobulin G [IgG] isotypes) (E). Group 2 had a bilateral iliac artery endothelial cell (EC)-seeded ePTFE interposition graft precoated with Matrigel. Three subgroups (A, B, and C) received a specific antibody against PDGF-BB, bFGF, or TGF-beta1. One (D) received all antibodies, and one served as control (nonimmune IgG isotypes) (E). Light microscopy and immunohistochemical stain showed that neointimal hyperplasia formation was significantly reduced in subgroups D compared to the others (p < 0.05). In subgroups D, the different precoating influenced neointimal hyperplasia formation. It was more pronounced in the prosthesis precoated with EC and Matrigel (p < 0.05). In organ culture, the amount of PDGF-BB, bFGF, and TGF-beta1 release was reduced in subgroup D animals compared to the others (p < 0.05). In subgroups D, the release of PDGF-BB, bFGF, and TGF-beta1 depended on ePTFE seeding. A higher amount of these growth factors was released in the prostheses precoated with EC and Matrigel (p < 0.05), and the bromodeoxyuridine labeling index confirmed higher incorporation in this subgroup (p < 0.001). The combined use of locally administered anti-PDGF-BB, bFGF, and TGF-beta1 monoclonal antibodies reduces neointimal hyperplasia formation.
Department of Surgery Pietro Valdoni, University of Rome La Sapienza, Policlinico Umberto I, Rome, Italy. paolo.sapienza@uniroma1.it
Paolo
P
Sapienza
Luca
L
di Marzo
Alessandra
A
Cucina
Valeria
V
Borrelli
Giovanni
G
Mosiello
Ursula
U
Basile
Simonetta
S
Iacovitti
Antonino
A
Cavallaro
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000077214:Becaplermin; D001807:Blood Vessel Prosthesis; D019917:Blood Vessel Prosthesis Implantation / Q000295:instrumentation*; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible; D003094:Collagen; D004338:Drug Combinations; D042783:Endothelial Cells / Q000378:metabolism / Q000637:transplantation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D006965:Hyperplasia; D007083:Iliac Artery / Q000378:metabolism / Q000601:surgery* / Q000648:ultrastructure; D007150:Immunohistochemistry; D007797:Laminin; D008855:Microscopy, Electron, Scanning; D023421:Models, Animal; D009924:Organ Culture Techniques; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D011138:Polytetrafluoroethylene; D011474:Prosthesis Design; D011509:Proteoglycans; D020574:Proto-Oncogene Proteins c-sis; D013552:Swine; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D017539:Tunica Intima / Q000378:metabolism / Q000601:surgery* / Q000648:ultrastructure
D000911:Antibodies, Monoclonal; D020099:Coated Materials, Biocompatible; D004338:Drug Combinations; D007797:Laminin; D010982:Platelet-Derived Growth Factor; D011509:Proteoglycans; D020574:Proto-Oncogene Proteins c-sis; D053773:Transforming Growth Factor beta1; D016222:Fibroblast Growth Factor 2; C059485:matrigel; D000077214:Becaplermin; D011138:Polytetrafluoroethylene; D003094:Collagen