Monocytes Induce Apoptosis of Vascular Smooth Muscle Cells via a Monocyte Chemoattractant Protein‐1 (MCP‐1) Mediated Mechanism

Abstract

Excessive apoptosis of smooth muscle cells (SMCs) contributes to pathogenesis of abdominal aortic aneurysm (AAA). We have previously demonstrated in a murine model of AAA that apoptotic SMCs stimulate vascular inflammation through production of MCP‐1. In the current study, we tested the hypothesis that MCP‐1 further induces cell death by enhancing the pro‐apoptotic capability of infiltrating inflammatory cells. Cultured mouse aortic SMCs and a mouse monocyte/macrophage cell line RAW264.7 were used. MCP‐1 (100ng/ml, 24h) primed RAWs elicited significant apoptosis of SMCs (2.21±0.349 fold increase in percentage of Annexin V‐PE+/7AAD− cells compared to untreated SMCs, n=5, p<0.05, ANOVA), while untreated RAWs or MCP‐1 had no effect. The pro‐apoptotic effect required cell‐cell contact or proximity between SMCs and RAWs because conditioned media made by MCP‐1 primed RAWs had minimal effect on apoptosis. In a CaCl2 induced murine aneurysm model, co‐staining with TUNEL and MOMA2 showed spatial correlation of apoptosis and monocyte/macrophage in aortic wall 7 days after AAA induction. In conclusion, our results suggest MCP‐1 may play a central role in pathogenesis of AAA. Produced by apoptotic SMCs and other cell types in injured vessels, MCP‐1 contributes directly to the recruitment of inflammatory cells and indirectly to induce apoptosis of SMCs.This work was supported by NIH grant R01HL088447‐01A2 (to B. Liu).