Guo Xiaobing, Saini Harjot K, Wang Jingwei, Gupta Suresh K, Goyal Ramesh K, Dhalla Naranjan S
University of Manitoba, Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre and Department of Physiology, Faculty of Medicine, Winnipeg, Canada.
Expert Rev Cardiovasc Ther. 2005 Jul;3(4):717-32. doi: 10.1586/14779072.3.4.717.
Ventricular remodeling subsequent to myocardial infarction (MI) is a complex process and is considered to be a major determinant of the clinical course of congestive heart failure (CHF). Emerging evidence suggests that activation of the renin-angiotensin system (RAS) plays an important role in post-MI ventricular remodeling; however, it is becoming clear that this is one of several neurohumoral systems that are activated in CHF. Blockade of RAS by angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor antagonists attenuates the ventricular dysfunction, but the effects of individual drugs in reducing the morbidity and mortality in CHF patients are variable. Furthermore, there is a difference of opinion as to the time of initiation of therapy with RAS blockers after the onset of MI. Since blockade of RAS partially improves cardiac function, it is suggested that a combination therapy involving RAS blockers (angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor antagonists) and agents that affect other neurohumoral systems may prove useful for improved treatment of CHF. Although activation of RAS has been shown to promote oxidative stress in experimental studies, the use of antioxidant therapy in CHF patients is controversial. Recent experimental studies have shown that ventricular remodeling in CHF is associated with remodeling of subcellular organelles such as sarcolemma, sarcoplasmic reticulum, myofibrils and extracellular matrix in terms of their molecular structure and composition. Since attenuation of remodeling in one and/or more subcellular organelles by different agents may prevent the progression of CHF, it is a challenge to develop specific drugs affecting molecular mechanisms associated with subcellular remodeling for the improved therapy of CHF.
心肌梗死（MI）后的心室重构是一个复杂的过程，被认为是充血性心力衰竭（CHF）临床病程的主要决定因素。新出现的证据表明，肾素-血管紧张素系统（RAS）的激活在心肌梗死后的心室重构中起重要作用；然而，越来越清楚的是，这只是在CHF中被激活的几种神经体液系统之一。用血管紧张素转换酶抑制剂或1型血管紧张素II受体拮抗剂阻断RAS可减轻心室功能障碍，但个别药物在降低CHF患者发病率和死亡率方面的效果各不相同。此外，对于心肌梗死后开始使用RAS阻滞剂治疗的时间也存在不同意见。由于阻断RAS可部分改善心脏功能，因此有人建议，涉及RAS阻滞剂（血管紧张素转换酶抑制剂或1型血管紧张素II受体拮抗剂）和影响其他神经体液系统的药物的联合治疗可能对改善CHF的治疗有用。尽管在实验研究中已表明RAS的激活会促进氧化应激，但在CHF患者中使用抗氧化治疗仍存在争议。最近的实验研究表明，CHF中的心室重构与肌膜、肌浆网、肌原纤维和细胞外基质等亚细胞器在分子结构和组成方面的重构有关。由于不同药物对一个和/或多个亚细胞器重构的减弱可能会阻止CHF的进展，因此开发影响与亚细胞重构相关分子机制的特异性药物以改善CHF的治疗是一项挑战。
