Inhibition of NF-κB improves left ventricular remodeling and cardiac dysfunction after myocardial infarction
Inhibition of NF-κB improves left ventricular remodeling and cardiac dysfunction after myocardial infarction
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DOI：
10.1152/ajpheart.00549.2006
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发表时间：
2007-01-01
影响因子：
4.8
通讯作者：
Isobe, Mitsuaki
中科院分区：
文献类型：
--
作者：
Onai, Yasuyuki;Suzuki, Jun-ichi;Isobe, Mitsuaki
抑制NF-κ B B可改善心肌梗死后左室重构和心功能不全美国生理学杂志心脏循环生理学292：H530-H538，2007年。首次发表于2006年8月18日; doi：10.1152/ajpheart. 00549.2006.-一些研究已经证明NF-κ B在很大程度上参与了心脏重塑的进展;然而，持续抑制NF-κ B是否能有效预防心肌重塑仍不确定。结扎大鼠左冠状动脉前支造成心肌梗死。IMD-0354（10 mg/kg/天），一种通过抑制IKK-β起作用的I κ B的新型磷酸化抑制剂，在诱导MI后24小时开始腹膜内注射，持续28天。28天后，IMD-0354治疗组显示出与媒介物治疗组相比显著改善的存活率（P < 0.05）。尽管两组的梗死面积相似，但左心室（LV）重构和舒张功能障碍改善，如LV腔变小所示（LV舒张末期面积：溶剂，74.13 +/- 3.57 mm（2）; IMD-0354，55.00 +/- 3.73 mm（2）; P < 0.05），早、晚充盈波峰值速度（E/A）比值较小（赋形剂，3.87 +/- 0.26; IMD-0354，2.61 +/- 0.24; P < 0.05），和较低的血浆脑钠肽水平（媒介物，167.63 +/-14.87 pg/ml; IMD- 0354，110.75 +/-6.41 pg/ml; P < 0.05）。此外，IMD-0354显著抑制非梗死心肌中的纤维化、巨噬细胞积聚和几种因子（转化生长因子-β 1、单核细胞趋化蛋白-1、基质金属蛋白酶-9和-2）的表达。结论：抑制NF-κ B B活化可减轻心肌梗死后的促炎反应，调节细胞外基质，为预防心肌梗死后不良心脏重构提供了一种有效途径。
Inhibition of NF-kappa B improves left ventricular remodeling and cardiac dysfunction after myocardial infarction. Am J Physiol Heart Circ Physiol 292: H530-H538, 2007. First published August 18, 2006; doi:10.1152/ajpheart. 00549.2006.-Several studies have demonstrated that NF-kappa B is substantially involved in the progression of cardiac remodeling; however, it remains uncertain whether the continuous inhibition of NF-kappa B is effective for the prevention of myocardial remodeling. Myocardial infarction (MI) was produced by ligation of the left anterior coronary artery of rats. IMD-0354 ( 10 mg/kg per day), a novel phosphorylation inhibitor of I kappa B that acts via inhibition of IKK-beta,was injected intraperitoneally starting 24 h after induction of MI for 28 days. After 28 days, the IMD-0354-treated group showed significantly improved survival rate compared with that of the vehicle-treated group (P < 0.05). Although infarct size was similar in both groups, improved left ventricular (LV) remodeling and diastolic dysfunction, as indicated by smaller LV cavity (LV end-diastolic area: vehicle, 74.13 +/- 3.57 mm(2); IMD-0354, 55.00 +/- 3.73 mm(2); P < 0.05), smaller peak velocity of early-to-late filling wave (E/A) ratio (vehicle, 3.87 +/- 0.26; IMD-0354, 2.61 +/- 0.24; P < 0.05), and lower plasma brain natriuretic peptide level (vehicle, 167.63 +/- 14.87 pg/ml; IMD- 0354, 110.75 +/- 6.41 pg/ml; P < 0.05), were observed in the IMD-0354-treated group. Moreover, fibrosis, accumulation of macrophages, and expression of several factors (transforming growth factor-beta 1, monocyte chemoattractant protein-1, matrix metalloproteinase-9 and -2) in the noninfarcted myocardium was remarkably inhibited by IMD-0354. In conclusion, inhibition of NF-kappa B activation may reduce the proinflammatory reactions and modulate the extracellular matrix and provide an effective approach to prevent adverse cardiac remodeling after MI.