The young mouse heart is composed of myocytes heterogeneous in age and function
The young mouse heart is composed of myocytes heterogeneous in age and function
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DOI：
10.1161/circresaha.107.151449
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发表时间：
2007-08-17
影响因子：
20.1
通讯作者：
Kajstura, Jan
中科院分区：
文献类型：
--
作者：
Rota, Marcello;Hosoda, Toru;Kajstura, Jan
成人心脏不断更新其肌细胞区室的认识提高了肌细胞的年龄和寿命与器官和生物体的年龄和寿命不一致的可能性。如果是这种情况，心肌细胞更新将导致在任何年龄的心肌组成的异质群体的实质细胞，结构上整合，但可能有助于不同的心肌性能。为了验证这一假设，从3个月大的小鼠中分离出左心室肌细胞，并测定这些细胞的收缩、电和钙循环特性以及衰老相关蛋白p16（INK 4a）和端粒长度的表达。心脏的特点是年轻，老年和衰老的心肌细胞共存。老年非复制性、p16（INK 4a）阳性、肥大、端粒严重缩短的心肌细胞与年轻、分裂中、p16 INK 4a阴性、端粒较长的小心肌细胞一起存在。在生理学上，动作电位（AP）时程和I-CaL在增强年轻心肌细胞的Ca ~（2+）循环和力学行为，或在减少衰老肥大细胞的Ca ~（2+）瞬变和性能中起着重要作用。AP的特性似乎受到瞬时外向K+电流I-to的调节，而瞬时外向K+电流I-to受K+通道亚基的不同表达的影响。总的来说，在生理和结构细胞水平上的这些观察结果证明，心脏必须不断地重新填充其肌细胞区室，以用更年轻更有效的细胞取代衰老的收缩不良的肌细胞。因此，心脏稳态和心肌细胞更新调节心脏功能。
The recognition that the adult heart continuously renews its myocyte compartment raises the possibility that the age and lifespan of myocytes does not coincide with the age and lifespan of the organ and organism. If this were the case, myocyte turnover would result at any age in a myocardium composed by a heterogeneous population of parenchymal cells which are structurally integrated but may contribute differently to myocardial performance. To test this hypothesis, left ventricular myocytes were isolated from mice at 3 months of age and the contractile, electrical, and calcium cycling characteristics of these cells were determined together with the expression of the senescence-associated protein p16(INK4a) and telomere length. The heart was characterized by the coexistence of young, aged, and senescent myocytes. Old nonreplicating, p16(INK4a)- positive, hypertrophied myocytes with severe telomeric shortening were present together with young, dividing, p16INK4a- negative, small myocytes with long telomeres. A class of myocytes with intermediate properties was also found. Physiologically, evidence was obtained in favor of the critical role that action potential ( AP) duration and I-CaL play in potentiating Ca2+ cycling and the mechanical behavior of young myocytes or in decreasing Ca2+ transients and the performance of senescent hypertrophied cells. The characteristics of the AP appeared to be modulated by the transient outward K+ current I-to which was influenced by the different expression of the K+ channels subunits. Collectively, these observations at the physiological and structural cellular level document that by necessity the heart has to constantly repopulate its myocyte compartment to replace senescent poorly contracting myocytes with younger more efficient cells. Thus, cardiac homeostasis and myocyte turnover regulate cardiac function.