Myosin heavy chain regulation and myocyte contractile depression after LV hypertrophy in aortic-banded mice

G. W. Dorn, J. Robbins, N. Ball, R. A. Walsh

Research output: Contribution to journalArticlepeer-review

104 Scopus citations

Abstract

Using an adult mouse aortic-banded model of pressure-overload hypertrophy and isolated cardiomyocyte mechanics studies, we examined the hypothesis that contractile depression is due to altered cardiac contractile proteins rather than changes in left ventricular (LV) geometry, loading, or the extracellular matrix. FVB mice were banded at the transverse aortic arch or sham operated and studied after 7 days. In nine animals the gradient across the aortic band averaged 47 ± 4 mmHg. Compared with sham-operated controls, banded animals had increased LV weight-to-body weight ratio (2.8 ± 0.1 and 3.5 ± 0.1, respectively; P = 0.035). Left ventricles from additional age-matched groups of mice that underwent identical surgical procedures were examined for altered transcriptional control of myosin heavy chains (MHCs). β-MHC protein content increased (15 ± 2%) vs. shams (3.8 ± 2%; P = 0.004). Dot blots of LV RNA showed a corresponding increase in β-MHC transcripts in banded animals (15.8 ± 2%) vs. controls (5.7 ± 2%; P = 0.012). Contractile performance was assessed using enzymatically disaggregated isolated LV myocytes paced at 0.5 Hz. There was no difference in percentage myocyte shortening between banded (8.6 ± 0.5%) and control (9.1 ± 0.5%) animals. However, maximal velocity of contraction was depressed after aortic banding (129 ± 11 vs. 233 ± 28 μm/s; P = 0.007), as was velocity of relaxation (105 ± 11 vs. 188 ± 22 μm/s; P = 0.007). These results suggest that depressed myocyte contractility after induction of pressure-overload hypertrophy in aortic-banded mice may be, in part, a consequence of transcriptional upregulation of the β-MHC.

Original languageEnglish
Pages (from-to)H400-H405
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume267
Issue number1 36-1
DOIs
StatePublished - 1994

Keywords

  • isolated myocytes
  • pressure-overload hypertrophy

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