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

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

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73 Scopus citations


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
Issue number2
StatePublished - Feb 1999
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by grant HL30696 from NIH (AMG). We are grateful to Suleman Said and Dr Tetsutaro Tamura for their technical support. The South Dakota Heart Research Foundation Cardiovascular Research Institute is a partnership between the University of South Dakota School of Medicine and Sioux Valley Hospitals and Health System.


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


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