Protein misfolding and cardiac disease

Establishing cause and effect

James S Pattison, Jeffrey Robbins

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Numerous neurodegenerative diseases are characterized by the accumulation of misfolded amyloidogenic proteins. Recent data indicate that a soluble pre-amyloid oligomer (PAO) may be the toxic entity in these diseases and the visible amyloid plaques, rather than causing the disease, may simply mark the terminal pathology. In prior studies, we observed PAO in the cardiomyocytes of many human heart failure samples. To test the hypothesis that cardiomyocyte-restricted expression of a known PAO is sufficient to cause heart failure, transgenic mice were created expressing polyglutamine repeats of 83 (PQ83) or 19 (PQ19). Long PQ repeats (> 50) form PAOs and result in neurotoxicity in Huntington's disease, whereas shorter PQ repeats are benign. PQ83 expression caused the intracellular accumulation of PAOs and aggregates leading to cardiomyocyte death and heart failure. Evidence of increased autophagy and necrosis accompanied the PQ83 cardiomyocyte pathology. The data confirm that protein misfolding resulting in intracellular PAO accumulation is sufficient to cause cardiomyocyte death and heart failure.

Original languageEnglish (US)
Pages (from-to)821-823
Number of pages3
JournalAutophagy
Volume4
Issue number6
DOIs
StatePublished - Aug 16 2008

Fingerprint

Proteostasis Deficiencies
Cardiac Myocytes
Heart Diseases
Amyloid
Heart Failure
Pathology
Amyloidogenic Proteins
Poisons
Huntington Disease
Autophagy
Amyloid Plaques
Neurodegenerative Diseases
Transgenic Mice
Cause of Death
Necrosis
Proteins

Keywords

  • Amyloid oligomer
  • Autophagy
  • Heart
  • Heart disease
  • Polyglutamine
  • Protein misfolding

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Protein misfolding and cardiac disease : Establishing cause and effect. / Pattison, James S; Robbins, Jeffrey.

In: Autophagy, Vol. 4, No. 6, 16.08.2008, p. 821-823.

Research output: Contribution to journalArticle

Pattison, James S ; Robbins, Jeffrey. / Protein misfolding and cardiac disease : Establishing cause and effect. In: Autophagy. 2008 ; Vol. 4, No. 6. pp. 821-823.
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