Desmin filaments and cardiac disease: Establishing causality

Xuejun Wang, Hanna Osinska, A. Martin Gerdes, Jeffrey Robbins

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Background: Gene targeting studies indicate that desmin is not required for embryonic myogenesis and heart formation but is essential for maintaining the structural and functional integrity of myocytes. Desmin-null mouse hearts developed hypertrophy and dilatation. However, the expression of desmin is very often upregulated rather than downregulated in many cardiac diseases. Altered distribution of desmin protein has been observed in dilated cardiomyopathy, as well as desminopathies to which a number of mutations of desmin and a missense mutation of αB-crystallin (CryAB) have been linked. Methods and Results: Using mouse transgenesis, we have recently demonstrated that modest overexpression of a mutant form of either desmin or CryAB in the heart leads to aberrant aggregation of desmin and CryAB proteins, disruption of the normal desmin network, perturbation of myofibril alignment, and distortion of the nuclear shape. The transgenic hearts develop concentric cardiac hypertrophy and diastolic malfunction at the early stage and ventricular dilatation and congestive heart failure subsequently. Moderate overexpression of either wild-type protein, however, did not cause discernible morphological and functional abnormalities or increased mortality. Conclusions: Thus cardiac overexpression of wild-type desmin is not detrimental whereas aberrant aggregation of desmin and disruption of the desmin network remodel the heart and compromise cardiac function.

Original languageEnglish (US)
Pages (from-to)S287-S292
JournalJournal of Cardiac Failure
Volume8
Issue number6 SUPPL.
DOIs
StatePublished - Dec 2002

Fingerprint

Desmin
Causality
Heart Diseases
Cardiomegaly
Dilatation
Gene Transfer Techniques
Crystallins
Proteins
Gene Targeting
Muscle Development
Myofibrils
Dilated Cardiomyopathy
Missense Mutation
Muscle Cells
Down-Regulation
Heart Failure

Keywords

  • Cardiomyopathy
  • Intermediate filaments
  • Protein aggregation
  • Ultrastructure
  • αB-crystallin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Desmin filaments and cardiac disease : Establishing causality. / Wang, Xuejun; Osinska, Hanna; Gerdes, A. Martin; Robbins, Jeffrey.

In: Journal of Cardiac Failure, Vol. 8, No. 6 SUPPL., 12.2002, p. S287-S292.

Research output: Contribution to journalArticle

Wang, Xuejun ; Osinska, Hanna ; Gerdes, A. Martin ; Robbins, Jeffrey. / Desmin filaments and cardiac disease : Establishing causality. In: Journal of Cardiac Failure. 2002 ; Vol. 8, No. 6 SUPPL. pp. S287-S292.
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