- 期刊
Upregulation of Myocardial Neutrophil Gelatinase-Associated Lipocalin during Development of Heart Failure Caused by Volume-Overload and the Effect in Regulating Activity of Matrix Metalloproteinase-9
摘要
Background: In patients with heart failure (HF), circulating neutrophil gelatinase-associated lipocalin (NGAL) level is increased, which is considered to be a predictor of mortality or renal outcomes. The expression of NGAL in the heart and kidney and its role in HF remain unclear. Methods: Aortocaval fistula was created in rats as a model of volume overload (VO)-induced HF. Results: During the development of HF, NGAL expression was upregulated in the heart but not in the kidney at both transcriptional and translational levels in the compensatory and HF phases, with a similar level in both phases. Cardiomyocytes were identified as the cell type responsible for NGAL expression. Consistent with the myocardial NGAL expression pattern, the plasma NGAL level was increased in both phases, and the level was not significantly different between both phases. We demonstrated the presence of a matrix metalloproteinase (MMP)-9/NGAL complex in cultured medium of cardiomyocytes isolated from volume-overloaded hearts by gelatin zymography. Formation of MMP-9/NGAL complex was shown to enhance the enzymatic activity of MMP-9. We found that early growth response (Egr)-1 was upregulated in the heart in both compensatory and HF phases. In neonatal cardiomyocytes, Egr-1 overexpression induced the gene expression of NGAL, which was dose-dependently suppressed by an interleukin-1 receptor antagonist. Conclusions: During the development of HF due to VO, NGAL was upregulated in the heart but not in the kidney in both compensatory and HF phases, with a similar expression level. Myocardial NGAL upregulation enhanced MMP-9 activity through formation of the MMP-9/NGAL complex. The expression of myocardial NGAL was regulated by Egr-1.
延伸閱讀
- Akbulut, M., Kutlu, M., Ozbay, Y., Polat, V., Bilen, M. N., Baydas, A., & Altas, Y. (2009). Efficacy of Clopidrogel on Reperfusion and High-Sensitivity C-Reactive Protein in Patients with Acute Myocardial Infarction. Mediators of Inflammation, 2009(), 620-624. https://doi.org/10.1155/2009/932515
- Lin, C. F. (2020). Investigation of the pathogenic factors for cardiac fibrosis after myocardial infarction and potential effects of histone deacetylase inhibitors on cardiac ischemia-reperfusion injury [doctoral dissertation, Taipei Medical University]. Airiti Library. https://www.airitilibrary.com/Article/Detail?DocID=U0007-2712201914422200
- Gelderman, M. P., Stuart, R., Vigerust, D., Fuhrmann, S., Lefkowitz, D. L., Allen, R. C., Lefkowitz, S. S., & Graham, S. (1998). Perpetuation of inflammation associated with experimental arthritis: the role of macrophage activation by neutrophilic myeloperoxidase. Mediators of Inflammation, 1998(), 381-389. https://doi.org/10.1080/09629359890758
- Wang, W. H., Hsiao, S. H., Chiou, K. R., Liu, C. P., Huang, W. C., Lin, S. K., Kuo, F. Y., Cheng, C. C., & Lin, K. L. (2012). Limited Efficacy of Myocardial Tissue Doppler for Predicting Left Ventricular Filling Pressure, Severe Pulmonary Edema, and Respiratory Failure in Acute Myocardial Infarction. Acta Cardiologica Sinica, 28(3), 206-215. https://www.airitilibrary.com/Article/Detail?DocID=10116842-201209-201209140012-201209140012-206-215
- Wagdy, S., Sobhy, M., & Loutfi, M. (2016). Neutrophil/Lymphocyte Ratio as a Predictor of In-Hospital Major Adverse Cardiac Events, New-Onset Atrial Fibrillation, and No-Reflow Phenomenon in Patients with ST Elevation Myocardial Infarction. Clinical Medicine Insights: Cardiology, 2016(), 19-22. https://doi.org/10.4137/CMC.S35555