Accelerated Migration and Proliferation of Smooth Muscle Cells Cultured from Neointima Induced by a Vena Cava Filter

Abstract

Formation of a neointima is associated with grafted artery or vein, angioplasty, and stent and inferior vena cava filter (IVCF) implantation. Contributing to the neointima is a population of vascular smooth muscle cells (SMC) that migrates from media and subsequently proliferates within intima. The purpose of this present study was to culture SMC from normal vessel wall and from neointima and to compare migration and growth of these cells. Neointima was stimulated in the vena cava of pigs by placement of an IVCF for 30 days. Tissue was taken from the thickened wall between the struts and from a normal segment of the IVCF. After removal of the endothelium and adventitia, explants were placed in culture dishes and were observed for the migration of cells. Immunoassay for smooth muscle alpha-actin was used to identify cell origin. Proliferation was determined by cell counting. The cell cycle regulator cyclin D1 was detected by Western blot analysis. SMC phenotype was confirmed by positive immunostaining for smooth muscle alpha-actin. Cells migrated from the neointimal explants (NI-SMC) more rapidly than cells from explants of normal media (NM-SMC). Proliferation of NI-SMC was also more rapid than NM-SMC with or without exogenous mitogens. NI-SMC expressed more cyclin D1 than NM-SMC. Injury to the vena cava triggered neointima formation characterized by the expansion of a population of SMC with increased migration and replication compared with SMC from normal regions of the vessel.