Institute of Physiology, Justus Liebig University, 35392 Giessen, Germany.
Department of Pharmacology and Pharmacotherapy, University of Szeged, 6722 Szeged, Hungary.
Int J Mol Sci. 2023 Mar 29;24(7):6443. doi: 10.3390/ijms24076443.
The cardiomyocyte-specific knockout (KO) of monoamine oxidase (MAO)-B, an enzyme involved in the formation of reactive oxygen species (ROS), reduced myocardial ischemia/reperfusion (I/R) injury in vitro. Because sex hormones have a strong impact on MAO metabolic pathways, we analyzed the myocardial infarct size (IS) following I/R in female and male MAO-B KO mice in vivo.
To induce the deletion of MAO-B, MAO-B KO mice (Myh6 Cre+/MAO-B) and wild-type (WT, Cre-negative MAO-B littermates) were fed with tamoxifen for 2 weeks followed by 10 weeks of normal mice chow. Myocardial infarction (assessed by TTC staining and expressed as a percentage of the area at risk as determined by Evans blue staining)) was induced by 45 min coronary occlusion followed by 120 min of reperfusion.
The mortality following I/R was higher in male compared to female mice, with the lowest mortality found in MAO-B KO female mice. IS was significantly higher in male WT mice compared to female WT mice. MAO-B KO reduced IS in male mice but had no further impact on IS in female MAO-B KO mice. Interestingly, there was no difference in the plasma estradiol levels among the groups.
The cardiomyocyte-specific knockout of MAO-B protects male mice against acute myocardial infarction but had no effect on the infarct size in female mice.
心肌细胞特异性敲除（KO）单胺氧化酶（MAO）-B，一种参与活性氧（ROS）形成的酶，可减少体外心肌缺血/再灌注（I / R）损伤。由于性激素对 MAO 代谢途径有很强的影响，我们分析了体内 MAO-B KO 小鼠的雌性和雄性 MAO-B KO 小鼠的心肌梗死面积（IS）。
为了诱导 MAO-B 的缺失，用他莫昔芬喂养 MAO-B KO 小鼠（Myh6 Cre + / MAO-B）和野生型（WT，Cre 阴性 MAO-B 同窝仔）2 周，然后正常喂养 10 周。通过 TTC 染色评估心肌梗死（用 Evans 蓝染色确定的危险区域的百分比表示），通过 45 分钟冠状动脉闭塞再灌注 120 分钟来诱导。
与雌性相比，雄性 I / R 后的死亡率更高，MAO-B KO 雌性的死亡率最低。与雌性 WT 相比，雄性 WT 小鼠的 IS 明显更高。MAO-B KO 降低了雄性小鼠的 IS，但对雌性 MAO-B KO 小鼠的 IS 没有进一步影响。有趣的是，各组之间的血浆雌二醇水平没有差异。
心肌细胞特异性敲除 MAO-B 可保护雄性小鼠免受急性心肌梗死，但对雌性小鼠的梗死面积无影响。
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