Sex Difference in Cardioprotection against Acute Myocardial Infarction in MAO-B Knockout Mice In Vivo

Abstract

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. Method and Results: To induce the deletion of MAO-B, MAO-B KO mice (Myh6 Cre+/MAO-Bfl/fl) and wild-type (WT, Cre-negative MAO-Bfl/fl 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. Results: 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. Conclusion: 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.

Health position paper and redox perspectives - Disease burden by transportation noise

“…Histamine co-localizes with norepinephrine in neurons [ 389 ] and is enclosed in cytoplasmic granules of mast cells, which lie adjacent to blood vessels and between cardiomyocytes [ 390 ], and mast cell degranulation might occur under stress conditions [ 391 ]. Activation of MAO contributed to development of endothelial dysfunction [ 392 ] and irreversible cardiomyocyte injury in vitro [ 393 ] and in vivo [ 394 ], also the latter was restricted to males only.…”

Recent advances on the role of monoamine oxidases in cardiac pathophysiology

“…More recently, cardiac-specific and tamoxifen-inducible MAO-B knockout mouse has been generated and also shown to present smaller infarct size following ischemia/reperfusion injury [ 21 ]. Moreover, the lack of MAO-B in mouse cardiomyocytes reduced the infarct size in male mice, whereas it remained ineffective in female mice [ 22 ]. Further studies are necessary to fully understand how cardiomyocyte MAO-B modulates signaling pathways underlying cardioprotection in male vs female mice.…”

Does Cell-Type-Specific Silencing of Monoamine Oxidase B Interfere with the Development of Right Ventricle (RV) Hypertrophy or Right Ventricle Failure in Pulmonary Hypertension?

“…A permanent cardiomyocyte-specific knockout of MAO-A reduces the incidence of catecholamine-induced arrhythmias in mice [ 26 ]. Recently, we demonstrated that a lack of cardiomyocyte-specific MAO-B reduces left ventricular infarct size in vitro [ 27 ] and in vivo [ 28 ]. Information on the importance of cardiomyocyte-specific MAOs in RV disease is absent.…”