TY - JOUR
T1 - Elevated circulating IL-32 presents a poor prognostic outcome in patients with heart failure after myocardial infarction
AU - Xuan, Wanling
AU - Huang, Weixing
AU - Wang, Ruijie
AU - Chen, Chang
AU - Chen, Yequn
AU - Wang, Yan
AU - Tan, Xuerui
N1 - Funding Information:
We greatly thank Dr. Ping Luo for giving advice on statistics. We would also like to thank Dr. Xiaojun Yu for additional experimental assistance. This study was supported by the National Natural Science Foundation of China (No. 81300125, to W.X.) and sponsored by the Shantou University Medical College Clinical Research Enhancement Initiative (201402, to W.X.).
Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/9/15
Y1 - 2017/9/15
N2 - Background Interleukin-32 (IL-32) is a newly discovered proinflammatory cytokine. However, there are limited data regarding IL-32 as a biomarker for heart failure (HF). In this study, we assessed the prognostic value of IL-32 in patients with chronic HF after myocardial infarction (MI). Methods and results Over a period of 1.8 years, we prospectively enrolled 100 patients with chronic HF after MI. IL-32, NT-proBNP, Matrix metallopeptidase 9 (MMP-9), procollagen type I (PI) and type III (PIII) were measured at baseline. Study endpoint was adverse cardiac events. High IL-32 levels were associated with numerous factors that are related to deteriorate cardiac function and cardiac fibrosis. Strong expression of IL-32 was detected in human cardiomyocytes from HF tissue. ROC curve revealed the area under the curve of IL-32 for predicting negative outcome of HF was 0.72 (95% CI: 0.60–0.83, P < 0.01). Kaplan–Meier statistics showed that the risk of adverse cardiac event was 5.75 fold (hazard ratio 5.75, 95% CI 1.53–21.58, P = 0.009), which increased in the highest quartile (> 296 pg/mL). Cox regression analysis revealed IL-32 was an independent predictor for cardiac events (hazard ratio 2.78, 95% CI 1.02–7.57, P = 0.046). Recombinant IL-32 significantly exacerbated infarct size in a mouse model of MI. IL-32 upregulated expression of MMP-9, PIII and transforming growth factor beta in rat fibroblasts. Conclusion IL-32 might be a novel predictor of adverse cardiac event in patients with HF after MI. The pro-fibrotic effect of IL-32 may contribute to adverse cardiac remodeling and progression to HF.
AB - Background Interleukin-32 (IL-32) is a newly discovered proinflammatory cytokine. However, there are limited data regarding IL-32 as a biomarker for heart failure (HF). In this study, we assessed the prognostic value of IL-32 in patients with chronic HF after myocardial infarction (MI). Methods and results Over a period of 1.8 years, we prospectively enrolled 100 patients with chronic HF after MI. IL-32, NT-proBNP, Matrix metallopeptidase 9 (MMP-9), procollagen type I (PI) and type III (PIII) were measured at baseline. Study endpoint was adverse cardiac events. High IL-32 levels were associated with numerous factors that are related to deteriorate cardiac function and cardiac fibrosis. Strong expression of IL-32 was detected in human cardiomyocytes from HF tissue. ROC curve revealed the area under the curve of IL-32 for predicting negative outcome of HF was 0.72 (95% CI: 0.60–0.83, P < 0.01). Kaplan–Meier statistics showed that the risk of adverse cardiac event was 5.75 fold (hazard ratio 5.75, 95% CI 1.53–21.58, P = 0.009), which increased in the highest quartile (> 296 pg/mL). Cox regression analysis revealed IL-32 was an independent predictor for cardiac events (hazard ratio 2.78, 95% CI 1.02–7.57, P = 0.046). Recombinant IL-32 significantly exacerbated infarct size in a mouse model of MI. IL-32 upregulated expression of MMP-9, PIII and transforming growth factor beta in rat fibroblasts. Conclusion IL-32 might be a novel predictor of adverse cardiac event in patients with HF after MI. The pro-fibrotic effect of IL-32 may contribute to adverse cardiac remodeling and progression to HF.
KW - Fibrosis
KW - Heart failure
KW - Interleukin-32
KW - Myocardial infarction
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U2 - 10.1016/j.ijcard.2017.03.065
DO - 10.1016/j.ijcard.2017.03.065
M3 - Article
C2 - 28747035
AN - SCOPUS:85025103589
SN - 0167-5273
VL - 243
SP - 367
EP - 373
JO - International Journal of Cardiology
JF - International Journal of Cardiology
ER -