Abstract 735: Fibulin-5 Inhibits Smooth Muscle Cells Proliferation And Migration, And Reduces Neointima Formation After Vascular Injury.
Background: Fibulin-5 is an extracellular matrix glycoprotein (~66kDa) that has a crucial role in elastin fibers organization and effects on cells attachment, proliferation and signal transduction. In this study, we investigated the role of fibulin-5 on regulating smooth muscle cells (SMC) proliferation and migration in vitro and neointima formation in vivo.
Methods: Fibulin-5 effect on SMC activity was tested in vitro on human primary venous SMC. SMC were exposed to exogenous fibulin-5 or were transduced with retroviral vectors to express the gene. The effect of fibulin-5 over-expression on SMC activity after vascular injury in vivo was tested in a rat carotid artery injury model using adenoviral vectors encoding fibulin-5 or GFP.
Results: Fibulin-5 significantly inhibits human primary venous SMC proliferation by ~20% and migration more than 35% with or without the presence of bFGF. In vivo, injured arteries that were exposed to adenoviral vectors encoding fibulin-5 had minimal proliferation while saline, or GFP infected arteries had significant neo-intimal formation at day 14 (intima/media ratio: 0.053±0.02, 1.44±0.32, and 1.08±0.37, respectively, p<0.0001). Ki-67 positive stained cells were abundant in the control vessels and scarce in the fibulin-5 treated arteries. The elastin membrane continuity was also measured as a marker of fibulin activity. Fibulin-5 treated arteries had significantly less elastic fibers defects (6.5±3.5% for fibulin-5 and 34±37% for saline treated arteries; p Value < 0.01).
Conclusions: These results suggest a direct inhibitory effect of fibulin-5 on human SMC proliferation and migration in vitro. These effects are translated in vivo to significant inhibition of neointima formation after vascular injury.