AJP - Heart and Circulatory Physiology, Vol 271, Issue 5 1978-H1987, Copyright © 1996 by American Physiological Society

ARTICLES

Role of microtubules in myocyte contractile dysfunction during cardiac hypertrophy in the rat

Y. Ishibashi, H. Tsutsui, S. Yamamoto, M. Takahashi, K. Imanaka-Yoshida, T. Yoshida, Y. Urabe, M. Sugimachi and A. Takeshita
Research Institute of Angiocardiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.

We have shown that increased microtubules cause 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 in 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 in 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 in 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.

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