Cystatin C increases in cardiac injury: A role in extracellular matrix protein modulation

Lifang Xie, Jerome Terrand, Beibei Xu, George Tsaprailis, Jean Boyer, Qin M. Chen

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Aims Numerous lines of evidence suggest a role of oxidative stress in initiation and progression of heart failure. We identify novel pathways of oxidative stress in cardiomyocytes using proteomic technology. Methods and results Cardiomyocytes and cardiac fibroblasts isolated from rat hearts were treated with sublethal doses of H2O2 for detection of secreted protein factors in the conditioned media by mass spectrometry-based proteomics. Comparison between the two cell types leads to the finding that H2O2 caused an elevated cystatin C protein in the conditioned medium from cardiomyocytes. When cardiomyopathy was induced in mice by chronic administration of doxorubicin, elevated cystatin C protein was detected in the plasma. Myocardial ischaemia by left anterior descending coronary artery occlusion causes an increase in the level of cystatin C protein in the plasma. In myocardial tissue from the ischaemic area, an increase in cystatin C correlates with the inhibition of cathepsin B activity and accumulation of fibronectin and collagen I/III. Overexpressing cystatin C gene or exposing fibroblasts to cystatin C protein results in an inhibition of cathepsin B and accumulation of fibronectin and collagen I/III. Conclusion Oxidants induce elevated cystatin C production from CMCs. Cystatin C plays a role in cardiac extracellular matrix remodelling.

Original languageEnglish (US)
Pages (from-to)628-635
Number of pages8
JournalCardiovascular Research
Volume87
Issue number4
DOIs
StatePublished - Sep 1 2010

Keywords

  • Cardiomyocytes
  • Cysteine protease inhibitor
  • Heart failure
  • Oxidative stress
  • Proteomics

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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