Homocysteine promotes p38-dependent chemotaxis in bovine aortic smooth muscle cells

Objective: Increased levels of homocysteine in the blood are a risk factor for atherosclerosis. The purpose of this study was to examine the effects of homocysteine on smooth muscle cell (SMC) migration and to determine whether p38 was involved in this process. Methods. The effect of 0.5 to 2.0 mmol/L D,L-homocysteine as a chemoattractant for SMCs was assayed with a modified Boyden chamber. To determine the functional role of p38 in SMC chemotaxis induced by D,L-homocysteine, we treated SMCs with a p38 inhibitor, SB203580, before the assay. Results. The number of migrated cells was increased 7.0 +/- 1.2-fold (n = 15; P <.001) by 2.0 mmol/L D,L-homocysteine. SB203580 partially prevented the migration of SMCs toward homocysteine. Preconditioning SMCs with 2.0 mmol/L D,L-homocysteine significantly enhanced chemotaxis toward 10% fetal bovine serum compared with nonconditioned control SMCs (28.9 +/- 3.3-fold vs 15.6 +/- 2.8-fold; P <.05). There was a fourfold p38 activation after exposure of SMCs to 2.0 mmol/L D,L-homocysteine by immunoblot. Conclusions. These results suggest that homocysteine not only is a chemoattractant for SMC but can also enhance SMC chemotactic potential. The mechanism of these effects may involve p38 activation.