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Abstract: Introduction: Following acute myocardial infarction (AMI), the acute inflammatory response contributes to wound healing but also to progressive myocardial injury. Interleukin-21 (IL-21) plays a key role in immunoregulation; whether IL-21 is associated with left ventricular (LV) remodelling after AMI is unknown. Methods: Plasma IL-21 concentrations were measured in 100 patients (age 58.9±12.0years, 77% male) admitted with AMI and LV dysfunction, at baseline (mean 46h) and again at 24weeks; cardiac magnetic resonance and measurement of B-type natriuretic peptide, monocyte chemoattractant protein-1, matrix metalloproteinase (MMP)-2, -3, -9, and tissue inhibitor of metalloproteinase (TIMP)-1, -2, -4 occurred at both time-points. Remodelling was defined as change in LV end-systolic volume index (ΔLVESVI). Results: Plasma IL-21 concentration was unchanged over time (48.1 [SD 35.4]pg/mL at baseline vs. 48.8 [61.3]pg/mL at 24weeks, p =0.92). Baseline IL-21 correlated significantly with ΔLVESVI (r =0.30, p =0.005) and change in LV end-diastolic volume index (r =0.33, p =0.003). On multivariate analysis, plasma IL-21 was an independent predictor of remodelling. IL-21 was also significantly associated with higher TIMP-4 concentrations and lower MMP-9 concentrations at baseline. Conclusions: IL-21 predicts adverse remodelling following AMI in patients with LV dysfunction. Whether it plays a direct pathophysiological role in remodelling merits further study. [Copyright &y& Elsevier]

Abstract: Introduction: Monocyte chemoattractant protein-1 (MCP-1) is elevated after acute myocardial infarction (AMI), and potentiates left ventricular (LV) remodeling in murine models of AMI. We examined the relationships between serum MCP-1, change in LV function and biomarkers related to remodeling in a cohort of AMI patients. Methods: Serum MCP-1 concentrations were measured in 100 patients (age 58.9±12.0years, 77% male) admitted with AMI and LV dysfunction, at baseline (mean 46h), 12 and 24weeks; cardiac magnetic resonance imaging and measurement of matrix metalloproteinase-2 (MMP-2), MMP-3 and MMP-9 occurred at each time-point. Results: MCP-1 increased significantly from 697 [483, 997]pg/mL at baseline to 878 [678, 1130]pg/mL at 24weeks (p <0.001). MMP-3 concentration increased while MMP-9 decreased significantly over time; MMP-2 concentration did not change significantly. Baseline MCP-1 correlated with change in (Δ) LV end-systolic volume index (ΔLVESVI; r =-0.48, p =0.01) and with ΔLV ejection fraction (ΔLVEF; r =0.50, p =0.02). However, ΔMCP-1 correlated positively with ΔLVESVI (r =0.40, p =0.006) and negatively with ΔLVEF (r =−0.36, p =0.004). MCP-1 had no relationship with any MMP. Conclusions: MCP-1 may have a dichotomous role following AMI, aiding early infarct healing but potentiating later remodeling, which merits further study before any therapeutic trials of MCP-1 modulation in humans. [Copyright &y& Elsevier]