Eto Y, Yonekura K, Sonoda M, Arai N, Sata M, Sugiura S, Takenaka K, Gualberto A, Hixon M L, Wagner M W, Aoyagi T
Department of Cardiovascular Medicine, University of Tokyo, Japan.
Circulation. 2000 May 9;101(18):2134-7. doi: 10.1161/01.cir.101.18.2134.
Calcineurin may play a pivotal role in the signaling of cardiac hypertrophy; since this hypothesis was first put forward, controversial reports have been published using various experimental models. This study was designed to compare the physiological left ventricular hypertrophy (LVH) induced by voluntary exercise with LVH induced by aortic constriction and to determine whether calcineurin participates in the signaling of exercise-induced LVH.
Wistar rats were assigned to 1 of the following 5 groups: 10 weeks of voluntary exercise (EX), a sedentary regimen, a 1-week (AC1) or 4-week (AC4) ascending aortic constriction period, or a sham operation. EX rats ran 2.4+/-0.7 km/day voluntarily in specially manufactured cages; this was associated with an increase of LV diastolic dimension and stroke volume. Myocardial calcineurin activity markedly increased in EX rats (46.4+/-8.3 versus 18.4+/-0.5 pmol. min(-1). mg(-1) in sedentary rats; P<0.001) and in AC1 rats (44.9+/-6.7 versus 22.1+/-3.7 pmol. min(-1). mg(-1) in sham-operated rats; P<0.001), but not in AC4 rats (29.0+/-3.4 pmol. min(-1). mg(-1)). Treatment with cyclosporin A completely inhibited the development of LVH in EX rats, but it only partially attenuated the development of LVH in AC4 rats.
Calcineurin was activated in exercise-induced physiological LVH and in the developing phase of LVH (AC1), but not in decompensated pressure-overload hypertrophy (AC4). Cyclosporin therapy for the prevention of LVH may be harmful because it does not block the development of pathological hypertrophy but rather that of favorable adaptive hypertrophy.
钙调神经磷酸酶可能在心肌肥大信号传导中起关键作用；自该假说首次提出以来，使用各种实验模型发表了有争议的报告。本研究旨在比较自愿运动诱导的生理性左心室肥大（LVH）与主动脉缩窄诱导的LVH，并确定钙调神经磷酸酶是否参与运动诱导的LVH信号传导。
将Wistar大鼠分为以下5组中的1组：10周自愿运动（EX）组、久坐不动组、1周（AC1）或4周（AC4）升主动脉缩窄期组或假手术组。EX组大鼠在特制笼子中每天自愿跑2.4±0.7公里；这与左心室舒张末期内径和每搏输出量增加有关。EX组大鼠（46.4±8.3对久坐大鼠的18.4±0.5 pmol·min⁻¹·mg⁻¹；P<0.001）和AC1组大鼠（44.9±6.7对假手术大鼠的22.1±3.7 pmol·min⁻¹·mg⁻¹；P<0.001）心肌钙调神经磷酸酶活性显著增加，但AC4组大鼠（29.0±3.4 pmol·min⁻¹·mg⁻¹）未增加。环孢素A治疗完全抑制了EX组大鼠LVH发展，但仅部分减弱了AC4组大鼠LVH发展。
钙调神经磷酸酶在运动诱导的生理性LVH和LVH发展阶段（AC1）被激活，但在失代偿性压力超负荷肥大（AC4）中未被激活。环孢素治疗预防LVH可能有害，因为它不阻止病理性肥大发展，而是阻止有利的适应性肥大发展。
