Smooth Muscle Cell Proliferation Is Proportional to the Degree of Balloon Injury in a Rat Model of Angioplasty

Abstract

Background A variable degree of smooth muscle cell (SMC) proliferation after balloon injury has been reported in previous rat studies. It is unknown whether balloon injury induces c- fos expression and whether it is related to the degree of vascular injury in vivo. Therefore, we tested the hypothesis that proportional increases in neointimal formation and c- fos expression might be present after different degrees of balloon dilation. Methods and Results Angioplasty of the carotid artery was performed with a balloon catheter. Vascular injury was evaluated at 0, 0.5, 1.0, 1.5, and 2 atm (n=6 for all). In 40 additional rats, total RNA dot blots were performed to assess the effect of various degrees of balloon injury on c- fos expression. SMC proliferation proportional to the increases of inflation pressure was found between 0 and 2 atm with neointimal areas of 0.002±0.002, 0.069±0.014, 0.128±0.043, 0.190±0.010, and 0.255±0.041 mm 2 , respectively. When the degree of SMC proliferation (neointima and neointima/media ratio) was plotted against balloon inflation pressure, a linear relation was observed ( r =.733, P <.001 and r =.755, P <.001, respectively). An increase in c- fos expression proportional to the degree of injury was found 30 minutes after injury. Conclusions Neointimal proliferation produced by balloon injury is related to balloon inflation pressure, supporting the concept of an SMC proliferative response proportional to the degree of injury. The increase in SMC proliferation is associated with a proportional increase in the early expression of the c- fos nuclear proto-oncogene.