Monocyte Chemotactic Protein-1-Interleukin-6-Osteopontin Pathway of Intra-Aneurysmal Tissue Healing.

BACKGROUND AND PURPOSE: We have previously demonstrated that the local delivery of monocyte chemotactic protein-1 (MCP-1) via an MCP-1-releasing poly(lactic-co-glycolic acid)-coated coil promotes intra-aneurysmal tissue healing. In this study, we demonstrate that interleukin-6 (IL-6) and osteopontin are downstream mediators in the MCP-1-mediated aneurysm-healing pathway. METHODS: Murine carotid aneurysms were created in C57BL/6 mice. Drug-releasing coils (MCP-1, IL-6, and osteopontin) and control poly(lactic-co-glycolic acid) coils were created and then implanted into the aneurysms to evaluate their intra-aneurismal-healing capacity. To investigate the downstream mediators for aneurysm healing, blocking antibodies for IL-6 receptor and osteopontin were given to the mice implanted with the MCP-1-releasing coils. A histological analysis of both murine and human aneurysms was utilized to cross-validate the data. RESULTS: We observed increased expression of IL-6 in MCP-1-coil-treated aneurysms and not in control-poly(lactic-co-glycolic acid)-only-treated aneurysms. MCP-1-mediated intra-aneurysmal healing is inhibited in mice given blocking antibody to IL-6 receptor. MCP-1-mediated intra-aneurysmal healing is also inhibited by blocking antibody to osteopontin. The role of IL-6 in intra-aneurysmal healing is in recruiting of endothelial cells and fibroblasts. Local delivery of osteopontin to murine carotid aneurysms via osteopontin-releasing coil significantly promotes intra-aneurysmal healing, but IL-6-releasing coil does not, suggesting that IL-6 cannot promote aneurysm healing independent of MCP-1. In the MCP-1-mediated aneurysm healing, osteopontin expression is dependent on IL-6; inhibition of IL-6 receptor significantly inhibits osteopontin expression in MCP-1-mediated aneurysm healing. CONCLUSIONS: Our findings suggest that IL-6 and osteopontin are key downstream mediators of MCP-1-mediated intra-aneurysmal healing.

Validation of a System to Predict Recanalization After Endovascular Treatment of Intracranial Aneurysms.

BACKGROUND: With increasing use of endovascular techniques in the treatment of ruptured and unruptured aneurysms, the issue of obliteration efficacy has become increasingly important. We have previously reported the Aneurysm Recanalization Stratification Scale, which uses accessible predictors including aneurysm-specific factors (size, rupture, and intraluminal thrombosis) and treatment-related features (treatment modality and immediate angiographic result) to predict retreatment risk after endovascular therapy. OBJECTIVE: To assess the external validity of the Aneurysm Recanalization Stratification Scale. METHODS: External validity was assessed in independent cohorts from 4 centers in the United States and Canada where endovascular and open neurovascular procedures are performed, and in a multicenter cohort of 1543 patients. Probability of retreatment stratified by risk score was derived for each center and the combined multicenter cohort. RESULTS: Despite moderate variability in retreatment rate among centers (29.5%, 9.9%, 9.6%, 26.3%, 19.7%, and 18.3%), the Aneurysm Recanalization Stratification Scale demonstrated good predictive value with C-statistics of 0.799, 0.943, 0.780, 0.695, 0.755, and 0.719 for each center and the combined cohort, respectively. Probability of retreatment stratified by risk score for the combined cohort is as follows: -2, 4.9%; -1, 5.7%; 0, 5.8%; 1, 13.1%; 2, 19.2%; 3, 34.9%; 4, 32.7%; 5, 73.2%; 6, 89.5%; and 7, 100.0%. CONCLUSION: Surgical decision-making and patient-centered informed consent require comprehensive and accessible information on treatment efficacy. The Aneurysm Recanalization Stratification Scale is a valid prognostic index. This is the first comprehensive model that has been developed to quantitatively predict retreatment risk following endovascular therapy.