Sterile Inflammation and Degradation Systems in Heart Failure

• Nishida Kazuhiko

  Cardiovascular Division, King’s College London British Heart Foundation Centre of Excellence

• Otsu Kinya

  Cardiovascular Division, King’s College London British Heart Foundation Centre of Excellence

Abstract

In most patients with chronic heart failure (HF), levels of circulating cytokines are elevated and the elevated cytokine levels correlate with the severity of HF and prognosis. Various stresses induce subcellular component abnormalities, such as mitochondrial damage. Damaged mitochondria induce accumulation of reactive oxygen species and apoptogenic proteins, and subcellular inflammation. The vicious cycle of subcellular component abnormalities, inflammatory cell infiltration and neurohumoral activation induces cardiomyocyte injury and death, and cardiac fibrosis, resulting in cardiac dysfunction and HF. Quality control mechanisms at both the protein and organelle levels, such as elimination of apoptogenic proteins and damaged mitochondria, maintain cellular homeostasis. An imbalance between protein synthesis and degradation is likely to result in cellular dysfunction and disease. Three major protein degradation systems have been identified, namely the cysteine protease system, autophagy, and the ubiquitin proteasome system. Autophagy was initially believed to be a non-selective process. However, recent studies have described the process of selective mitochondrial autophagy, known as mitophagy. Elimination of damaged mitochondria by autophagy is important for maintenance of cellular homeostasis. DNA and RNA degradation systems also play a critical role in regulating inflammation and maintaining cellular homeostasis mediated by damaged DNA clearance and post-transcriptional regulation, respectively. This review discusses some recent advances in understanding the role of sterile inflammation and degradation systems in HF.

Journal

• Circulation Journal

  Circulation Journal 81 (5), 622-628, 2017

  The Japanese Circulation Society

Keywords

• Autophagy
• Inflammation
• Mitochondria
• Nucleic acid degradation
• Protein degradation

Details

• CRID: 1390001205108725120
• NII Article ID: 130005612036
• NII Book ID: AA11591968
• DOI: 10.1253/circj.cj-17-0261
• ISSN: 13474820
• ISSN: 13469843
• NDL BIB ID: 028129070
• PubMed: 28381696
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I028129070
• Web Site: https://www.jstage.jst.go.jp/article/circj/81/5/81_CJ-17-0261/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2017381419
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed