Ishibashi Y, Tsutsui H, Yamamoto S, Takahashi M, Imanaka-Yoshida K, Yoshida T, Urabe Y, Sugimachi M, Takeshita A
Research Institute of Angiocardiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Am J Physiol. 1996 Nov;271(5 Pt 2):H1978-87. doi: 10.1152/ajpheart.1996.271.5.H1978.
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.
我们已经表明，在猫右心室压力超负荷肥大中，微管增加会导致心肌细胞收缩功能障碍。为了研究心脏肥大进展与微管之间的关联，并阐明微管在肥大心肌细胞收缩缺陷中的作用，我们使用蛋白质免疫印迹分析和免疫荧光显微镜评估了游离和聚合微管蛋白的量，并评估了从压力超负荷左心室（LV）肥大的大鼠中分离出的心肌细胞的肌节力学。施加压力超负荷后，LV中的总微管蛋白和聚合微管蛋白逐渐且持续增加。微管增加与肥大的发展和进展相关，而不是对心肌应激负荷的即时反应。肥大心肌细胞的收缩功能随着微管的增加而平行降低。微管解聚使最初降低的LV心肌细胞收缩功能恢复正常。因此，由于心肌持续压力超负荷导致LV肥大期间微管密度的逐渐增加可能会导致随之而来的心肌细胞收缩功能障碍。
