Genetic silencing of pacemaker cells: local intervention with global implications.
Genetic silencing of pacemaker cells: local intervention with global implications.
复制标题
DOI：
10.1161/jaha.112.001412
复制
发表时间：
2012-04
影响因子：
5.4
通讯作者：
Akar FG
中科院分区：
文献类型：
--
作者：
Karam CS;Akar FG
心力衰竭是一种主要的公共卫生流行病，每年仅在美国就夺去数十万人的生命。尽管在许多心血管疾病的管理和预防方面取得了重要进展，但随着人口的老龄化，心力衰竭的发病率和患病率正在增加。现有的治疗心力衰竭患者的方法远不是最佳的，而且往往与心律失常的活动和心脏性猝死的风险有关。因此，为这些患者寻找新颖、有效和安全的治疗选择是我国和世界其他地区未满足需求的关键领域。在本期《美国心脏协会杂志》（JAHA）上发表的一项概念验证研究中，Lugenbiel等人描述了一种新的基于基因的方法，可以通过靶向心房结内的离散细胞群来潜在地治疗心力衰竭。来自实验和临床研究的几条证据表明，控制心率是心力衰竭治疗的重要目标。事实上，心力衰竭患者的平均心率和心血管疾病发病率之间有很强的联系。在临床试验中，某种心力衰竭治疗降低总死亡率的能力，在某些情况下，是通过其降低心率的功效来预测的。此外，心率升高和心力衰竭之间的因果关系可以概括为这样一个事实：在没有其他危险因素或损伤的情况下，持续的心动过速是心室重构的一个既定机制，最终导致心力衰竭的发生。在实验室里，许多研究小组利用了心率升高和左心室之间的关系
Heart failure is a major public health epidemic that claims hundreds of thousands of lives annually in the United States alone. Despite important advances in the management and prevention of many cardiovascular disorders, the incidence and prevalence of heart failure are increasing with the aging of the population. Existing treatments for patients with heart failure are far from being optimal and are often associated with proarrhythmic activity and risk of sudden cardiac death. Therefore, the search for novel, effective, and safe therapeutic options for these patients represents a critical area of unmet need for this country and the rest of the world. In an elegant proof of concept study published in this issue of the Journal of the American Heart Association (JAHA), Lugenbiel et al1 describe a novel gene-based approach for potentially treating heart failure by targeting discrete cell populations within the sino-atrial node.Several lines of evidence derived from experimental and clinical studies indicate that a controlled heart rate is an important target for heart failure therapy. 2 In fact, a strong link between average heart rate and cardiovascular morbidity in patients with heart failure has been documented. In clinical trials the ability of a given heart failure treatment to reduce overall mortality is, in some cases, predicted by its heart rate lowering efficacy. Moreover, a causative relation between elevated heart rate and heart failure is epitomized by the fact that sustained tachycardia, in the absence of other risk factors or insults, is a well-established mechanism of ventricular remodeling that culminates in the onset of heart failure. 3 In the experimental laboratory, numerous groups have exploited the relation between elevated heart rate and left ventricular