Tumor necrosis factor-alpha produced in cardiomyocytes mediates a predominant myocardial inflammatory response to stretch in early volume overload

作者：Chen, Yuanwen; Pat, Betty; Zheng, Junying; Cain, Laura; Powell, Pamela; Shi, Ke; Sabri, Abdelkarim; Husain, Ahsan; Dell'Italia, Louis J^*

来源：Journal of Molecular and Cellular Cardiology, 2010, 49(1): 70-78.

DOI：10.1016/j.yjmcc.2009.12.013

• Tumor necrosis factor-alpha
• Myocardial inflammation
• Mast cells
• Cardiac myocytes
• Volume overload

Acute stretch caused by volume overload (VO) of aorto-caval fistula (ACF) induces a variety of myocardial responses including mast cell accumulation, matrix metalloproteinase (MMP) activation, and collagen degradation, all of which are critical in dictating long-term left ventricle (LV) outcome to VO Meanwhile, these responses can be part of myocardial inflammation dictated by tumor necrosis factor-alpha (TNF-alpha), which is elevated after acute ACF. However, it is unknown whether TNF-alpha mediates a major myocardial inflammatory response to stretch in early VO In 24-h ACF and sham rats, microarray gene expression profiling and subsequent Ingenuity Pathway Analysis identified a predominant inflammatory response and a gene network of biologically interactive genes strongly linked to TNF-alpha. Western blot demonstrated increased local production of TNF-alpha in the LV (1 71- and 1 66-fold in pro- and active-TNF-alpha over control, respectively, P<0.05) and cardiomyocytes (2- and 4-fold in pro- and active-TNF-alpha over control, respectively. P<0.05) TNF-alpha neutralization with infliximab (5.5 mg/kg) attenuated the myocardial inflammatory response to acute VO, as indicated by inhibition of inflammatory gene upregulation, myocardial infiltration (total CD45 cells, mast cells, and neutrophils), MMP-2 activation, collagen degradation, and cardiac cell apoptosis, without improving LV remodeling and function These results indicate that TNF-alpha produced by cardiomyocytes mediates a predominant inflammatory response to stretch in the early VO in the ACF rat, suggesting an important role of TNF-alpha in initiating pathophysiological response of myocardium to VO. Published by Elsevier Ltd.

• 出版日期2010-7
• 单位上海交通大学