TUMOR-NECROSIS-FACTOR-ALPHA CAN MODULATE THE PHENOTYPE OF AORTIC SMOOTH-MUSCLE CELLS

In culture, rabbit aortic smooth muscle cells (SMC) from an atheroma d iffered phenotypically from SMC from normal media (M-SMC) in their gro wth rate, secretion of SMC-derived growth factor (SDGF), and metabolis m of acetylated low density lipoproteins (a-LDL). The factor responsib le for this in vivo phenotypic change of SMC was investigated in vitro . After preincubation of M-SMC with 0.1-10 U ml-1 of tumour necrosis f actor-alpha (TNF) for 1-3 days, the cells grew faster than control cel ls and secreted a substantial amount of SDGF. The population doubling time and secretion of SDGF were inversely correlated. Moreover, after preincubation with TNF, the SMC metabolized [I-125]a-LDL, unlike contr ol M-SMC. These findings show that TNF can modulate the phenotype of S MC and suggest that it is important in the pathogenesis of atheroscler osis.