Tumour necrosis factor-alpha can modulate the phenotype of aortic smooth muscle cells.
In culture, rabbit aortic smooth muscle cells (SMC) from an atheroma differed phenotypically from SMC from normal media (M-SMC) in their growth rate, secretion of SMC-derived growth factor (SDGF), and metabolism of acetylated low density lipoproteins (a-LDL). The factor responsible 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 factor-alpha (TNF) for 1-3 days, the cells grew faster than control cells 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 [125I]a-LDL, unlike control M-SMC. These findings show that TNF can modulate the phenotype of SMC and suggest that it is important in the pathogenesis of atherosclerosis.
Second Department of Internal Medicine, School of Medicine, Chiba University, Japan.
N
N
Morisaki
Q P
QP
Xu
T
T
Koshikawa
Y
Y
Saito
S
S
Yoshida
S
S
Ueda
D000818:Animals; D001011:Aorta / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D006133:Growth Substances / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D010641:Phenotype; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D006133:Growth Substances; D008077:Lipoproteins, LDL; D014409:Tumor Necrosis Factor-alpha; D004247:DNA