›› 2012, Vol. 32 ›› Issue (12): 1571-.doi: 10.3969/j.issn.1674-8115.2012.12.012

• Original article (Basic research) • Previous Articles     Next Articles

Effect of eplerenone on expression of MMP-2 in cardiac fibroblasts stimulated by high glucose and IL-1β

CHI Ju-fang1, GUO Hang-yuan1, TANG Wei-liang1, LÜ|Hai-tao1, ZHOU Yan1, Hiroyasu UZUI2   

  1. 1.Department of Cardiology, Shaoxing People's Hospital, Shaoxing 312000, China； 2.Affiliated Hospital of Faculty of Medical Sciences, University of Fukui, Fuku 910-1193, Japan
  • Online:2012-12-28 Published:2012-12-31
  • Supported by:

    Natural Science Foundation of Zhejiang Province, Y2100535；Tradition Chinese Medicine Research Foundation of Zhejiang Province, 2011ZB151

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Abstract:

Objective To investigate the effect of eplerenone on the expression of matrix metalloproteinase-2 (MMP-2) in cardiac fibroblasts stimulated by high glucose and interleukin (IL)-1β. Methods Human cardiac fibroblasts were cultured in fluid with normal glucose (normal control group), high glucose (high glucose group) and iso-osmotic mannitol (hyperosmotic control group) in the absence or presence of IL-1β and/or eplerenone. The activity of MMP-2 in the supernatant was assessed by gel zymography, and the expression of MMP-2 mRNA and tissue inhibitor of metalloproteinase-2 (TIMP-2) mRNA was determined by RT-PCR. Results The activity of MMP-2 and MMP-2 mRNA in high glucose group and hyperosmotic control group were significantly higher than those in normal control group (P<0.01, P<0.05), while the activity of MMP-2 and MMP-2 mRNA in hyperosmotic control group were significantly lower than those in high glucose group (P<0.05). There was a twofold increase in the activity of MMP-2 and expression of MMP-2 mRNA in high glucose+IL-1β group as compared with high glucose group. The activity of MMP-2 and expression of MMP-2 mRNA in high glucose+eplerenone group and normal control+IL-1β+eplerenone group were significantly lower than those in high glucose group and normal control+IL-1β group (P<0.05). Conclusion High glucose may increase the activity of MMP-2 and expression of MMP-2 mRNA in human cardiac fibroblasts through osmotic and non-osmotic pathways, which may be enhanced by IL-1β and inhibited by eplerenone.

Key words: high glucose, interleukin-1β, matrix metalloproteinase-2, mineralocorticoid receptor antagonist, fibroblast