Monocyte chemotactic protein-1 gene expression in smooth muscle cells cultures derived from human coronary artery lesions

Monocyte chemotactic protein-1 (MCP-1), a monocyte specific cytokine. is believed to play an important role in the early mechanism of monocyte infiltration as a part of the inflammatory response to vascular injury. Its role in the process of restenosis remains unknown. We postulated that MCP-1 is present in de novo and restenotic lesions, and its expression by smooth muscle cells (S'MC) may in turn be mediated by other cytokines and growth factors. Methods: Atherectomy specimens were obtained from 84 patients with de novo and from 16 patients with restenotic lesions. Sixteen SMC cultures (8 de novo and 8 restenotic lesions) were studied. Total RNA was isolated from unstimulated cultures and from cultures submitted to 6 hours challenge with platelet derived growth factor (PDGF). tumor necrosis factor alpha (TNFa) insulin-like growth factor-1 (IGF-1) and angiotensin (All). Northern Blot technique was utilized to assess MCP-1 gene expression. Autoradiographs were scanned and digitized using Image 1.55f NIH software. Results: MCP-1 gene expression was present in SMC cultures derived from both: de novo and restenotic human coronary artery lesions. Basal gene level in SMC cultures from restenotic lesions was upregulated when compared with de novo lesions (p<0.002). The expression of MCP-1 in SMC cultures derived from de novo lesions was significantly increased after stimulation with: PDGF (p<0.05), TNFa (p<0.001 ), IGF-l'(p<O.OI). and All (p<0.01). Basal MCP-1 levels in SMC cultures derived from restenotic lesion was upregulated to the degree that further challenge was negligible. Thus. MCP-1. may play an important role in coronary restenosis process.