The old heart: operating on the edge.
The old heart: operating on the edge.
复制标题
老心：在边缘运作。
DOI：
10.1002/0470868694.ch15
复制
发表时间：
2001
影响因子：
--
通讯作者：
Pepe,S
中科院分区：
文献类型：
--
作者：
Lakatta,EG;Sollott,SJ;Pepe,S
心肌细胞的兴奋伴随着Ca 2+内流，其触发胞质[Ca 2 +]（Cai）和收缩的瞬时增加。虽然Ca 2+负荷的程度，Ca 2+的瞬态和收缩的幅度增加，过量的Ca 2+负荷导致失调的Ca 2+稳态，受损的收缩，心律失常和细胞死亡。细胞Ca 2+负荷由膜结构和渗透性特征、通过膜内蛋白质的调节功能调节Ca 2+流入或流出的刺激强度以及影响膜结构和功能的活性氧（ROS）决定。衰老心脏的心肌细胞在刺激（生理或药理学）期间表现出过度Ca 2+负荷的病理表现的阈值降低，这增加了Ca 2+内流，例如响应于神经递质、缺血后再灌注或氧化应激。细胞“重塑”是衰老心脏中心细胞相对Ca 2+不耐受的一个原因;细胞大小增加，调节Ca 2+处理的蛋白质的量发生变化，部分原因是基因表达改变;另一个原因是Ca 2+调节蛋白所在的膜组成的变化，例如膜ω6：ω 3多不饱和脂肪酸（PUFA）的增加;第三个原因是细胞内产生ROS的可能性增加。这些决定因素的每一类都会随着衰老而变化，并降低老年心脏发生Ca 2+超载的阈值。通过基因治疗恢复Ca 2+调节蛋白，通过饮食逆转膜ω6：ω 3 PUFA失衡，或通过抗氧化剂，可以潜在地降低衰老心脏内过量Ca 2+负荷的风险。
Excitation of cardiac cells is accompanied by Ca2+influx which triggers a transient increase in cytosolic [Ca2+], (Cai), and contraction. While the amplitudes of the Caitransient and contraction increase with the extent of cell Ca2+loading, excess Ca2+loading leads to dysregulation of Ca2+homeostasis, impaired contraction, arrhythmia and cell death. The cell Ca2+load is determined by membrane structure and permeability characteristics, the intensity of stimuli that modulate Ca2+influx or efflux via regulatory function of proteins within membranes, and reactive oxygen species (ROS), which affect both membrane structure and function. Cardiocytes of senescent hearts exhibit a reduced threshold for pathologic manifestations of excess Ca2+loading during stimulation (physiologic or pharmacologic) that increases Ca2+influx, e.g. in response to neurotransmitters, post‐ischaemic reperfusion, or oxidative stress. Cell ‘remodelling’ is one cause of the relative Ca2+intolerance of cardiocytes in the senescent heart; cells increase in size and changes occur in the amounts of proteins that regulate Ca2+handling due, in part, to altered gene expression; another cause is a change in the composition of membranes in which Ca2+regulatory proteins reside, e.g. an increase in membrane ω6:ω3polyunsaturated fatty acids (PUFA); a third cause is an enhanced likelihood for intracellular generation of ROS. Each class of these determinants changes with ageing and reduces the threshold for Ca2+overload to occur with the older heart. The risk of excess Ca2+loading within the senescent heart can potentially be reduced by gene therapy to restore Ca2+regulatory proteins, by diet to reverse the membrane ω6:ω3PUFA imbalance, or by antioxidants.