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

Myocardial short-range force responses increase with age in F344 rats.
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F344 大鼠的心肌短程力反应随着年龄的增长而增加。

DOI:
10.1016/j.yjmcc.2008.10.004
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发表时间:
2009
影响因子:
5
通讯作者:
Campbell,KennethS
Campbell,KennethS
中科院分区:
医学2区
文献类型:
--
作者:
Mitov,MihailI;Holbrook,AnastasiaM;Campbell,KennethS

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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 l0is the initial muscle length) in preparations from 4-month-old animals to 0.49±0.01% l0in 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.