Landmesser Ulf, Wollert Kai C, Drexler Helmut
Deparment of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany.
Cardiovasc Res. 2009 Feb 15;81(3):519-27. doi: 10.1093/cvr/cvn317. Epub 2008 Nov 19.
Left ventricular (LV) remodelling remains an important treatment target in patients after myocardial infarction (MI) and chronic heart failure (CHF). Accumulating evidence has supported the concept that beneficial effects of current pharmacological treatment strategies to improve the prognosis in these patients, such as angiotensin-converting enzyme (ACE) inhibition, angiotensin type 1 receptor blocker therapy, and beta-blocker therapy, are related, at least in part, to their effects on LV remodelling and dysfunction. However, despite modern reperfusion therapy after MI and optimized treatment of patients with CHF, LV remodelling is observed in a substantial proportion of patients and is associated with an adverse clinical outcome. These observations call for novel therapeutic strategies to prevent or even reverse cardiac remodelling. Recent insights from experimental studies have provided new targets for interventions to prevent or reverse LV remodelling, i.e. reduced endothelial nitric oxide (NO) synthase-derived NO availability, activation of cardiac and leukocyte-dependent oxidant stress pathways, inflammatory pathway activation, matrix-metalloproteinase activation, or stem cell transfer and delivery of novel paracrine factors. An important challenge in translating these observations from preclinical studies into clinical treatment strategies relates to the fact that clinical studies are designed on top of established pharmacological therapy, whereas most experimental studies have tested novel interventions without concomitant drug regimens such as ACE inhibitors or beta-blockers. Therefore, animal studies may overestimate the effect of potential novel treatment strategies on LV remodelling and dysfunction, since established pharmacological therapies may act, in part, via identical or similar signalling pathways. Nevertheless, preclinical studies provide essential information for identifying potential novel targets, and their potential drawbacks, and are required for developing novel clinical treatment strategies to prevent or reverse LV remodelling and dysfunction.
左心室（LV）重构仍然是心肌梗死（MI）后患者和慢性心力衰竭（CHF）患者的重要治疗靶点。越来越多的证据支持这样一个概念，即目前用于改善这些患者预后的药物治疗策略，如血管紧张素转换酶（ACE）抑制、1型血管紧张素受体阻滞剂治疗和β受体阻滞剂治疗，其有益效果至少部分与其对左心室重构和功能障碍的影响有关。然而，尽管心肌梗死后采用了现代再灌注治疗以及对慢性心力衰竭患者进行了优化治疗，但仍有相当一部分患者出现左心室重构，且与不良临床结局相关。这些观察结果呼吁采用新的治疗策略来预防甚至逆转心脏重构。实验研究的最新见解为预防或逆转左心室重构的干预提供了新靶点，即内皮型一氧化氮（NO）合酶衍生的NO可用性降低、心脏和白细胞依赖性氧化应激途径激活、炎症途径激活、基质金属蛋白酶激活，或干细胞转移及新型旁分泌因子的递送。将这些临床前研究的观察结果转化为临床治疗策略的一个重要挑战在于，临床研究是在既定的药物治疗基础上设计的，而大多数实验研究在没有ACE抑制剂或β受体阻滞剂等伴随药物方案的情况下测试了新型干预措施。因此，动物研究可能高估了潜在新型治疗策略对左心室重构和功能障碍的影响，因为既定的药物治疗可能部分通过相同或相似的信号通路起作用。尽管如此，临床前研究为识别潜在的新靶点及其潜在缺点提供了重要信息，并且对于开发预防或逆转左心室重构和功能障碍的新型临床治疗策略是必需的。
