The role of the proteasome in heart disease

Yi Fan Li, Xuejun Wang

Research output: Contribution to journalReview article

32 Citations (Scopus)

Abstract

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
Volume1809
Issue number2
DOIs
StatePublished - Feb 1 2011

Fingerprint

Proteasome Endopeptidase Complex
Heart Diseases
Ubiquitin
Myocarditis
Cardiomegaly
Cardiac Myocytes
Quality Control
Transgenic Mice
Quality control
Heart Failure
Muscle
Fluorescence
Pharmacology
Pressure
Cells
Wounds and Injuries
Chemical analysis
Proteins

Keywords

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

ASJC Scopus subject areas

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

Cite this

The role of the proteasome in heart disease. / Li, Yi Fan; Wang, Xuejun.

In: Biochimica et Biophysica Acta - Gene Regulatory Mechanisms, Vol. 1809, No. 2, 01.02.2011, p. 141-149.

Research output: Contribution to journalReview article

@article{3a372aa4cb9d418fabf3d4d77993fe9c,
title = "The role of the proteasome in heart disease",
abstract = "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.",
keywords = "Cardiac hypertrophy, Desmin-related cardiomyopathy, Diabetes, Heart disease, Myocardial ischemia, Myocarditis, Proteasome",
author = "Li, {Yi Fan} and Xuejun Wang",
year = "2011",
month = "2",
day = "1",
doi = "10.1016/j.bbagrm.2010.09.001",
language = "English (US)",
volume = "1809",
pages = "141--149",
journal = "Biochimica et Biophysica Acta - Gene Regulatory Mechanisms",
issn = "1874-9399",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - The role of the proteasome in heart disease

AU - Li, Yi Fan

AU - Wang, Xuejun

PY - 2011/2/1

Y1 - 2011/2/1

N2 - 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.

AB - 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.

KW - Cardiac hypertrophy

KW - Desmin-related cardiomyopathy

KW - Diabetes

KW - Heart disease

KW - Myocardial ischemia

KW - Myocarditis

KW - Proteasome

UR - http://www.scopus.com/inward/record.url?scp=79251541786&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79251541786&partnerID=8YFLogxK

U2 - 10.1016/j.bbagrm.2010.09.001

DO - 10.1016/j.bbagrm.2010.09.001

M3 - Review article

VL - 1809

SP - 141

EP - 149

JO - Biochimica et Biophysica Acta - Gene Regulatory Mechanisms

JF - Biochimica et Biophysica Acta - Gene Regulatory Mechanisms

SN - 1874-9399

IS - 2

ER -