Myocardial short-range force responses increase with age in F344 rats

Mihail I. Mitov, Anastasia M. Holbrook, Kenneth S. Campbell

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

The mechanical properties of triton-permeabilized ventricular preparations isolated from 4, 18 and 24-month-old F344 rats were analyzed to provide information about the molecular mechanisms that lead to age-related increases in diastolic myocardial stiffness in these animals. Passive stiffness (measured in solutions with minimal free Ca2+) did not change with age. This implies that the aging-associated dysfunction is not due to changes in titin or collagen molecules. Ca2+-activated preparations exhibited a characteristic short-range force response: force rose rapidly until the muscle reached its elastic limit and less rapidly thereafter. The elastic limit increased from 0.43 ± 0.01% l0 (where l0 is the initial muscle length) in preparations from 4-month-old animals to 0.49 ± 0.01% l0 in preparations from 24-month-old rats (p < 0.001, ANOVA). Relative short-range force was defined as the maximum force produced during the short-range response normalized to the prevailing tension. This parameter increased from 0.110 ± 0.002 to 0.142 ± 0.002 over the same age-span (p < 0.001, ANOVA). Analytical gel electrophoresis showed that the maximum stiffness of the preparations during the short-range response and the relative short-range force increased (p = 0.031 and p = 0.005 respectively) with the relative content of slow β myosin heavy chain molecules. Elastic limit values did not correlate with myosin isoform content. Simulations based on these results suggest that attached β myosin heavy chain cross-bridges are stiffer than links formed by α myosin heads. In conclusion, elevated content of stiffer β myosin heavy chain molecules may contribute to aging-associated increases in myocardial stiffness.

Original languageEnglish
Pages (from-to)39-46
Number of pages8
JournalJournal of Molecular and Cellular Cardiology
Volume46
Issue number1
DOIs
StatePublished - Jan 2009

Bibliographical note

Funding Information:
This work was supported by the American Heart Association Scientist Development Grant 0630079N, NIH AG021862, NIH HL 090749 (all to KSC) and the University of Kentucky Research Challenge Trust Fund.

Keywords

  • Contractile proteins
  • Detergent skinned muscle
  • Diastolic dysfunction
  • Mathematical modeling
  • Myosin
  • Ventricular function
  • Ventricular stiffness

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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