Role of microtubules for the myocyte contractile dysfunction during
cardiac hypertrophy in the rat.
Ishibashi, Yuji, Hiroyuki Tsutsui, Shimako Yamamoto, Masaru Takahashi,
Kyoko Imanaka-Yoshida, Toshimichi Yoshida, Yoshitoshi Urabe, Masaru
Sugimachi, and Akira Takeshita.
Research Institute of Angiocardiology and Cardiovascular Clinic,
Faculty of Medicine, Kyushu University, Fukuoka 812, Department of
Pathology, Mie University, Tsu, Mie 514 and Department of Circulatory
Dynamics, National Cardiovascular Center, Suita, Osaka 565, Japan
APStracts 3:0263H, 1996.
We have shown that the increased microtubules cause the myocyte
contractile dysfunction in feline right ventricular pressure overload
hypertrophy. To investigate the association between the progression
of cardiac hypertrophy and microtubules and to delineate the role of
microtubules for the contractile defects in hypertrophied myocytes,
we assessed the amounts of free and polymerized tubulin proteins
using Western blot analysis and immunofluorescence micrograph and
evaluated the sarcomere mechanics of myocytes isolated from rats with
pressure overload left ventricular (LV) hypertrophy. Total and
polymerized tubulins were progressively and persistently increased in
LV after the imposition of pressure overload. The increase of
microtubules was associated with the development and progression of
hypertrophy and not the immediate response to the stress loading to
the myocardium. The contractile function of hypertrophied myocytes
was depressed in parallel with the increase of microtubules.
Depolymerization of microtubules normalized the initially depressed
LV myocyte contractile function. Thus the progressive increase of
microtubule density during LV hypertrophy due to persistent pressure
overloading to the myocardium may cause the consequent myocyte
contractile dysfunction.
Received 6 November 1995; accepted in final form 8 May 1996.
APS Manuscript Number H1035-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 July 96