Molecular basis of electrical remodeling in atrial fibrillation
Molecular basis of electrical remodeling in atrial fibrillation
复制标题
DOI：
10.1006/jmcc.2000.1147
复制
发表时间：
2000-06-01
影响因子：
5
通讯作者：
Nerbonne, JM
中科院分区：
文献类型：
--
作者：
Van Wagoner, DR;Nerbonne, JM
心房颤动 (AF) 是最常见的心律失常，通常与其他心血管疾病相关。房颤可导致血栓栓塞、左心室功能下降和中风，而且重要的是，它与死亡率增加独立相关。 AF 是一种进行性疾病；大量证据表明，疾病进展是心房累积的电生理和结构重塑的结果。人们对描述 AF 患者心房重塑所涉及的分子机制非常感兴趣。细胞电生理学研究表明，慢性 AF 患者心房肌细胞中 L 型电压门控 Ca2+ 电流 (I-Ca,I-L)、瞬时外向 K+ 电流 (I-TO) 和超快速延迟整流 K+ 电流 (I-Kur) 的密度显着降低。在从 AF 犬模型中分离出的肌细胞中，电流的类似（但不相同）变化很明显，在这种情况下，电流的变化与潜在通道形成亚基的表达减少相关。在人类和犬类 AF 中，I-Ca、I-L 的减少似乎足以解释观察到的动作电位持续时间和有效不应期的减少，而动作电位持续时间和有效不应期是重塑心房的特征。此外，肌浆网 Ca2+ ATP 酶的表达减少，表明 AF 中钙循环受到影响。这些最近的研究表明，钙超载和钙处理扰动在房颤诱发的心房重塑中发挥着重要作用。尽管已经取得了相当大的进展，但显然有必要进行进一步的研究，重点关注确定人类以及 AF 动物模型中 AF 不同阶段所伴随的详细结构、细胞和分子变化。预计从这些研究中收集到的分子见解将有助于开发改进的治疗方法来治疗 AF 并预防心律失常的进展。 (C) 2000 年学术出版社。
Atrial fibrillation (AF) is the most common cardiac arrhythmia, and is often associated with other cardiovascular disorders and diseases. AF can lead to thromboembolism, reduced left ventricular function and stroke, and, importantly, it is independently associated with increased mortality. AF is a progressive disease; numerous lines of evidence suggest that disease progression results from cumulative electrophysiological and structural remodeling of the atria. There is considerable interest in delineating the molecular mechanisms involved in the remodeling that occurs in the atria of patients with AF. Cellular electrophysiological studies have revealed marked reductions in the densities of the L-type voltage-gated Ca2+ current, I-Ca,I-L, the transient outward K+ current, I-TO, and the ultrarapid delayed rectifier K+ current, I-Kur, in atrial myocytes from patients in chronic AF. Similar (but not identical) changes in currents are evident in myocytes isolated from a canine model of AF and, in this case, the changes in currents are correlated with reduced expression of the underlying channel forming subunits. In both human and canine AF, the reduction in I-Ca,I-L, appears to be sufficient to explain the observed decreases in action potential duration and effective refractory period that are characteristic features of the remodeled atria. In addition, expression of the sarcoplasmic reticulum Ca2+ ATPase is reduced, suggesting that calcium cycling is affected in AF. These recent studies suggest that calcium overload and perturbations in calcium handling play prominent roles in AF-induced atrial remodeling. Although considerable progress has been made, further studies focused on defining the detailed structural, cellular and molecular changes that accompany the different stages of AF in humans, as well as in animal models of AF, are clearly warranted. It is anticipated that molecular insights gleaned from these studies will facilitate the development of improved therapeutic approaches to treat AF and to prevent the progression of the arrhythmia. (C) 2000 Academic Press.