TRANSFORMING GROWTH-FACTOR-BETA-1 INHIBITS HUMAN ARTERIAL SMOOTH-MUSCLE CELL-PROLIFERATION IN A GROWTH-RATE-DEPENDENT MANNER

BACKGROUND: Proliferation of arterial smooth-muscle cells is central i n the development of both atherosclerosis and intimal hyperplasia. The cytokine transforming growth factor-beta 1 (TGF-Beta 1) is known to h ave variable effects on smooth-muscle cell proliferation, Using human arterial smooth-muscle cells, we sought (1) to define the serum concen trations required to maintain cellular proliferation; and (2) to defin e the effects of TGF-Beta 1 on smooth-muscle cell proliferation, METHO DS: Smooth-muscle cell cultures were established from the normal aorta of transplant donors. Cells were grown to subconfluent and confluent densities, then incubated in either serum-free media, or 1% or 10% fet al bovine serum (FBS) enhanced media, Cellular proliferation was assay ed by cell counting at 24, 48, and 96 hours to establish growth rate, Identical experiments with the addition of recombinant human TGF-Beta 1 (5 ng/mL) were also performed, Studies were done in triplicate for e ach group, and results expressed as the mean +/- SE, Groups were compa red by analysis of variance. RESULTS: In subconfluent cultures, only s mooth-muscle cells in 10% FBS proliferated, whereas growth arrest occu rred in serum-free media and 1% FBS. In confluent cultures, cells in a ll media conditions proliferated, TGF-Beta 1 had an inhibitory effect in actively proliferating cultures. There was a positive correlation b etween the inhibitory effects of TGF-Beta 1 and smooth-muscle cell gro wth rate (r = .65; P = 0.005). CONCLUSIONS: When confluent, human arte rial smooth-muscle cells continue to proliferate after serum deprivati on, suggesting that these cells are capable of conditioning their own medium, inhibits smooth-muscle cell proliferation in a growth-rate-dep endent manner. These data suggest that TGF-Beta 1 may have a growth-re gulatory role in vascular disease by counteracting states of arterial smooth-muscle cell proliferation.