Potential role of a new anti-beta3 integrin antibody in the development of intimal hyperplasia after vascular surgery: an in vitro smooth muscle cell model.
The occurrence of intimal hyperplasia after vascular surgery is an ongoing concern in current clinical practice. Among the many factors involved in the development of this pathology, platelet adhesion and myointimal proliferation play a major role. Both these processes are mediated by integrins (mainly alphavbeta3 integrins). Over the past years, several substances have been designed to delay or inhibit the cell proliferation that leads to hyperplasia and mainly include monoclonal antibodies directed against integrins. The aim of the present study was to evaluate the effects of an antibody denoted P37 (anti beta3 integrin) on human smooth muscle cells (SMC) and its role in blocking the B3 subunit. To this end, SMC from human umbilical artery were cultured in the presence or absence of the cell substrate vitronectin (VN) and incubated with P37. After 4 days of treatment, determination was made of cell proliferation and migration. Smooth muscle cells grown on VN showed increased proliferation and migration compared to control VN-free cultures. However, the presence of P37 in the culture medium inhibited proliferation and reduced migration. Combined treatment with VN and P37 led to improved proliferation but VN was unable to reverse the effects on migration observed in the former cultures. Results suggest that in vitro, P37 is capable of blocking human SMC beta3 integrins and thus impedes cell proliferation and migration These findings may have clinical implications related to modulation of the development of hyperplasia.
Gimeno
M J
MJ
Department of Morphological Sciences and Surgery, Alcala University, Madrid, Spain.
González
J
J
Rodríguez
M
M
Corrales
C
C
Bellón
J M
JM
Buján
J
J
D000906:Antibodies / Q000008:administration & dosage*; D015703:Antigens, CD / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D006965:Hyperplasia; D066298:In Vitro Techniques; D039661:Integrin beta3; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D014656:Vascular Surgical Procedures / Q000009:adverse effects*; D019096:Vitronectin / Q000494:pharmacology
D000906:Antibodies; D015703:Antigens, CD; D039661:Integrin beta3; D010980:Platelet Membrane Glycoproteins; D019096:Vitronectin