Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, Jiangsu, People's Republic of China.
Mol Biol Rep. 2010 Oct;37(7):3067-72. doi: 10.1007/s11033-009-9879-6. Epub 2009 Nov 12.
Endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) may play an important role in attenuating cardiac remodeling and apoptosis after myocardial infarction. However, the anti-inflammation effects of eNOS in infarcted myocardium and the role of MAPK signaling in eNOS/NO mediated cardiac remodeling have not yet been elucidated. Adenovirus carrying Human eNOS gene was delivered locally into heart 4 days prior to induction of myocardial infarction (MI) by left anterior descending coronary artery ligation. Monocyte/macrophage infiltration was detected by ED-1 immunohistochemistry. Western blot was employed to examine the activation of MAPK. eNOS gene transfer significantly reduced myocardial infarct size and improved cardiac contractility as well as left ventricle (LV) diastolic function at 7 days after MI. In addition, eNOS gene transfer decreased monocyte/macrophage infiltration in the infarct region of the heart. Phosphorylation of MAPK after MI were also dramatically reduced by eNOS gene transfer. All the protective effects of eNOS were blocked by N(ω)-nitro-L-arginine methyl ester (L-NAME) administration, indicating a NO-mediated event. These results demonstrate that the eNOS/NO system provides cardiac protection after MI injury through inhibition of inflammation and suppression of MAPK signaling.
内皮型一氧化氮合酶（eNOS）和一氧化氮（NO）可能在减轻心肌梗死后的心脏重构和细胞凋亡中发挥重要作用。然而，eNOS 在梗死心肌中的抗炎作用以及 MAPK 信号通路在 eNOS/NO 介导的心脏重构中的作用尚未阐明。通过结扎左前降支冠状动脉，在诱导心肌梗死（MI）前 4 天将携带人 eNOS 基因的腺病毒局部递送至心脏。通过 ED-1 免疫组织化学检测单核细胞/巨噬细胞浸润。采用 Western blot 检测 MAPK 的激活。eNOS 基因转移可显著减少心肌梗死面积，并改善 MI 后 7 天的心脏收缩功能和左心室（LV）舒张功能。此外，eNOS 基因转移可减少梗死区心脏中的单核细胞/巨噬细胞浸润。MI 后 MAPK 的磷酸化也被 eNOS 基因转移显著降低。eNOS 抑制剂 N（ω）-硝基-L-精氨酸甲酯（L-NAME）给药阻断了 eNOS 的所有保护作用，表明这是一种依赖于 NO 的事件。这些结果表明，eNOS/NO 系统通过抑制炎症和抑制 MAPK 信号通路，为 MI 损伤后的心脏提供保护。
