Circulation, Vol 90, 533-555, Copyright © 1994 by American Heart Association
H Tsutsui, H Tagawa, RL Kent, PL McCollam, K Ishihara, M Nagatsu and G Cooper 4th
Cardiac hypertrophy in response to systolic pressure overloading frequently
results in contractile dysfunction, the cause for which has been unknown.
Since, in contrast, the same degree and duration of hypertrophy in response
to systolic volume overloading does not result in contractile dysfunction,
we postulated that the contractile dysfunction of pressure hypertrophied
myocardium might result from a direct effect of stress as opposed to strain
loading on an intracellular structure of the hypertrophied cardiocyte. The
specific hypothesis tested here is that the microtubule component of the
cytoskeleton is such an intracellular structure, which, forming in excess,
impedes sarcomere motion. The feline right ventricle was either pressure
overloaded by pulmonary artery banding or volume overloaded by atrial
septotomy. The quantity of microtubules was estimated from immunoblots and
immunofluorescent micrographs, and their mechanical effects were assessed
by measuring sarcomere motion during microtubule depolymerization. We show
here that stress loading increases the microtubule component of the cardiac
muscle cell cytoskeleton; this apparently is responsible for the entirety
of the cellular contractile dysfunction seen in our model of
pressure-hypertrophied myocardium. No such effects were seen in right
ventricular cardiocytes from normal or volume-overloaded cats or in left
ventricular cardiocytes from any group of cats. Importantly, the linked
microtubule and contractile abnormalities are persistent and thus may be
found to have significance for the deterioration of initially compensatory
cardiac hypertrophy into the congestive heart failure state.
ARTICLES
Role of microtubules in contractile dysfunction of hypertrophied cardiocytes
Department of Medicine, Medical University of South Carolina, Charleston.
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