Systemic inflammation as a predictor of clinical outcomes after lower extremity angioplasty/stenting

Abstract

The activation state of the systemic inflammatory milieu has been proposed as a critical regulator of vascular repair after injury. We evaluated the early inflammatory response after endovascular intervention for symptomatic peripheral arterial disease to determine its association with clinical success or failure. Blood samples were obtained from 14 patients undergoing lower extremity angioplasty/stenting and analyzed using high-throughput gene arrays, multiplex serum protein analyses, and flow cytometry. Time-dependent plasma protein and monocyte phenotype analyses demonstrated endovascular revascularization had a modest influence on the overall activation state of the systemic inflammatory system, with baseline variability exceeding the perturbations induced by the intervention. In contrast, specific time-dependent changes in the monocyte genome are evident in the initial 28days, predominately in those genes associated with leukocyte extravasation. Investigating the relationship between inflammation and the 1-year success or failure of the intervention showed no single plasma protein was correlated with outcome, but a more comprehensive cluster analysis revealed a clear pattern of protein expression that was closely related to the clinical phenotype. Corresponding examination of the monocyte genome identified a gene subset at 1day postprocedure that was predictive of clinical outcome, with most of these genes active in cell-cycle signaling. Although the global influence of angioplasty/stenting on systemic inflammation was modest, circulating cytokine and monocyte genome analyses support a pattern of early inflammation that is associated with ultimate intervention success vs failure. Molecular profiles incorporating genes involved in monocyte cell-cycle progression and homing, or proinflammatory cytokines, or both, offer the most promise for the development of class prediction tools for clinical application.