Wanling Xuan1, Weixing Huang1, Ruijie Wang1, Chang Chen1, Yequn Chen1, Yan Wang2, Xuerui Tan3. 1. Department of Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China. 2. Department of Radiology, University of California San Francisco, San Francisco, CA, United States. 3. Department of Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China. Electronic address: tanxuerui@vip.sina.com.
Abstract
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 1.8years, 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 (>296pg/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.
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 1.8years, 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 (>296pg/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.
Authors: Dominik Jenča; Vojtěch Melenovský; Josef Stehlik; Vladimír Staněk; Jiří Kettner; Josef Kautzner; Věra Adámková; Peter Wohlfahrt Journal: ESC Heart Fail Date: 2020-12-14