TIMP-2 modulates neointimal formation in experimental ePTFE arterial grafts.
BACKGROUND
In vascular reconstructive surgery, myointimal hyperplasia contributes to the adverse outcome of synthetic grafts. This phenomenon is because of unregulated extracellular matrix degradation and remodeling, and excessive smooth muscle cell proliferation and migration. Matrix metallopreoteinase 2 (MMP-2) is known as an important contributor to these events. The aims of our study was to investigate the effects of selective MMP-2 inhibitor (TIMP-2) in endothelialization rate, SMC proliferation, and myointimal hyperplasia in experimental ePTFE arterial grafts.


METHODS
In 20 male Lewis rats, a 1-cm long ePTFE graft has been inserted at the level of the abdominal aorta. Animals were randomized in two groups (10 animals each): group A received six subcutaneous inoculations of TIMP-2 (2.5 microg) after surgery, group B received only the vehicle of TIMP-2.


RESULTS
Neointimal thickness, as well as SMC density, were augmented in group B, whereas endothelial cells density was augmented in group A, and these findings were statistically significant. In group A SMC were better organized, just like SMC of thoracic aorta. In group B SMC were no organized. Furthermore, anti-TIMP-2 and anti-MMP-2 coloration revealed higher levels of TIMP-2 and lower levels of MMP-2 in group A versus group-B.


CONCLUSIONS
Use of TIMP-2 affects the neointimal formation of experimental e-PTFE arterial grafts, leading to a better-organized neointima, with improved endothelialization.
Cavallaro
Giuseppe
G
Department of Surgery P. Valdoni, University La Sapienza, Rome, Italy. cavallaro@uniromal.it
Cucina
Alessandra
A
Randone
Bruto
B
Polistena
Andrea
A
Mosiello
Giovanni
G
Coluccia
Pierpaolo
P
De Toma
Giorgio
G
Cavallaro
Antonino
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D001807:Blood Vessel Prosthesis; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D005109:Extracellular Matrix / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000276:immunology / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D011138:Polytetrafluoroethylene; D011183:Postoperative Complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology / Q000601:surgery
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D061965:Matrix Metalloproteinase Inhibitors; D019716:Tissue Inhibitor of Metalloproteinase-2; D011138:Polytetrafluoroethylene; D020778:Matrix Metalloproteinase 2