The role of the proteasome in heart disease

Yi Fan Li, Xuejun Wang

Research output: Contribution to journalReview articlepeer-review

44 Scopus citations


Intensive investigations into the pathophysiological significance of the proteasome in the heart did not start until the beginning of the past decade but exciting progress has been made and summarized here as two fronts. First, strong evidence continues to emerge to support a novel hypothesis that proteasome functional insufficiency represents a common pathological phenomenon in a large subset of heart disease, compromises protein quality control in heart muscle cells, and thereby acts as a major pathogenic factor promoting the progression of the subset of heart disease to congestive heart failure. This front is represented by the studies on the ubiquitin-proteasome system (UPS) in cardiac proteinopathy, which have taken advantage of a transgenic mouse model expressing a fluorescence reporter for UPS proteolytic function. Second, pharmacological inhibition of the proteasome has been explored experimentally as a potential therapeutic strategy to intervene on some forms of heart disease, such as pressure-overload cardiac hypertrophy, viral myocarditis, and myocardial ischemic injury. Not only between the two fronts but also within each one, a multitude of inconsistencies and controversies remain to be explained and clarified. At present, the controversy perhaps reflects the sophistication of cardiac proteasomes in terms of the composition, assembly, and regulation, as well as the intricacy and diversity of heart disease in terms of its etiology and pathogenesis. A definitive role of altered proteasome function in the development of various forms of heart disease remains to be established.

Original languageEnglish (US)
Pages (from-to)141-149
Number of pages9
JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Issue number2
StatePublished - Feb 2011
Externally publishedYes


  • Cardiac hypertrophy
  • Desmin-related cardiomyopathy
  • Diabetes
  • Heart disease
  • Myocardial ischemia
  • Myocarditis
  • Proteasome

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics


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