Chronic pressure overload cardiac hypertrophy and failure in guinea pigs: II. Cytoskeletal remodeling

Xuejun Wang, Li Faqian, Scott E. Campbell, A. Martin Gerdes

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

The cytoskeleton is a major regulator of cell shape. To explore potential mechanisms for maladaptation of cardiac myocyte shape in pressure overload-induced congestive heart failure, the abundance and organization of major intra- and extra-myofibrillar cytoskeleton of cardiac myocytes were examined with western blotting and confocal microscopy in guinea pigs with chronic aortic stenosis. It was found that: (1) the amount and distribution of α-actinin and myomesin remained unchanged at both the compensated hypertrophy and the congestive heart failure stages: (2) loss of titin was associated with myocyte lengthening in heart failure; (3) desmin protein and filaments in LV myocytes increased progressively with mechanical overload cardiac hypertrophy and subsequent heart failure; (4) a newly developed and validated quantitative confocal microscopic approach disclosed that the microtubule density in isolated LV myocytes increased by 21% at 4 weeks and by 48% 6 months after aortic constriction; (5) at the heart failure stage, microtubule density in LV myocytes showed a statistically significant inverse correlation to the LV maximum + dP/dt and a direct correlation to LV myocyte lengthening; (6) the increased microtubule density in LV myocytes in this model was not due to an increase in total tubulin; and (7) microtubule density in left atrial and right ventricular myocytes also increased when they underwent hypertrophy secondary to left heart failure. These results suggest that the down-regulation of titin and up-regulation of microtubule and desmin filaments may contribute to myocyte lengthening and malfunction in pressure overload congestive heart failure.

Original languageEnglish (US)
Pages (from-to)319-331
Number of pages13
JournalJournal of Molecular and Cellular Cardiology
Volume31
Issue number2
DOIs
StatePublished - Feb 1999

Keywords

  • Cardiac hypertrophy
  • Cardiac myocytes
  • Congestive heart failure
  • Cytoskeleton
  • Desmin
  • Microtubules
  • Myomesin
  • Pressure overload
  • Titin
  • α-actinin

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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