Der Sarkissian Shant, Grobe Justin L, Yuan Lihui, Narielwala Dhruv R, Walter Glenn A, Katovich Michael J, Raizada Mohan K
Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Hypertension. 2008 Mar;51(3):712-8. doi: 10.1161/HYPERTENSIONAHA.107.100693. Epub 2008 Feb 4.
Angiotensin converting enzyme 2 (ACE2) has been linked to cardiac dysfunction and hypertension-induced cardiac pathophysiology. In this study, we used a gene overexpression approach to investigate the role of ACE2 in cardiac function and remodeling after myocardial infarction. Rats received an intracardiac injection of 4.5x10(8) lentivirus containing ACE2 cDNA, followed by permanent coronary artery ligation (CAL) of the left anterior descending artery. At 24 hours and 6 weeks after surgery, cardiac functions, viability, and pathophysiology were assessed by MRI) and by histological analysis. At 24 hours post-CAL, left ventricular (LV) anterior wall motion was stunted to the same extent in control CAL and lenti-ACE2-treated CAL rats. However lenti-ACE2-treated CAL rats showed a 60% reduction in delayed contrast-enhanced LV volume after gadodiamide injection, indicating early ischemic protection of myocardium by ACE2. At 6 weeks after CAL, lenti-ACE2 rats demonstrated a complete rescue of cardiac output, a 41% rescue of ejection fraction, a 44% rescue in contractility, a 37% rescue in motion, and a 53% rescue in LV anterior (infracted) wall thinning compared with control CAL rats. No changes were observed in the LV posterior (noninfarcted) wall other than an 81% rescue in motion produced by ACE2 in CAL rats. Finally, infarct size measured by 2,3,5-triphenyl-tetrazolium chloride staining was not significantly different between the ligated groups. These observations demonstrate that cardiac overexpression of ACE2 exerts protective influence on the heart during myocardial infarction by preserving cardiac functions, LV wall motion and contractility, and by attenuating LV wall thinning.
血管紧张素转换酶2（ACE2）与心脏功能障碍以及高血压诱导的心脏病理生理学有关。在本研究中，我们采用基因过表达方法来研究ACE2在心肌梗死后心脏功能和重塑中的作用。大鼠接受心内注射含有ACE2 cDNA的4.5×10⁸慢病毒，随后对左前降支动脉进行永久性冠状动脉结扎（CAL）。在手术后24小时和6周，通过MRI以及组织学分析评估心脏功能、活力和病理生理学。在CAL后24小时，对照CAL大鼠和慢病毒-ACE2处理的CAL大鼠的左心室（LV）前壁运动同样受到抑制。然而，慢病毒-ACE2处理的CAL大鼠在注射钆双胺后延迟对比增强的LV体积减少了60%，表明ACE2对心肌有早期缺血保护作用。在CAL后6周，与对照CAL大鼠相比，慢病毒-ACE2大鼠的心输出量完全恢复，射血分数恢复41%，收缩力恢复44%，运动恢复37%，LV前（梗死）壁变薄恢复53%。除了CAL大鼠中ACE2使LV后（未梗死）壁运动恢复81%外，未观察到其他变化。最后，通过2,3,5-三苯基氯化四氮唑染色测量的梗死面积在结扎组之间没有显著差异。这些观察结果表明，ACE2在心脏中的过表达通过保留心脏功能、LV壁运动和收缩力以及减轻LV壁变薄，在心肌梗死期间对心脏发挥保护作用。
