Journal article

Publication year: 2021

Pages: 14-23

Journal: Free Radical Biology and Medicine

Volume number: 165

ISSN: 0891-5849

eISSN: 1873-4596

Open access status: Hybrid

DOI Link: https://doi.org/10.1016/j.freeradbiomed.2021.01.020

Publisher: Elsevier

Abstract: 

Monoamine oxidase B (MAO-B), a protein localized at the outer mitochondrial membrane, catalyzes the oxidative deamination of biogenic amines thereby producing reactive oxygen species (ROS). Increased ROS formation contributes to myocardial ischemia/reperfusion (I/R); however, the importance of different ROS producing enzymes for increased I/R-induced ROS formation and the subsequent I/R injury is still a matter of debate. Here we describe the first cardiomyocytes-specific MAO-B knockout mouse and test the hypothesis that lack of cardiomyocyte MAO-B protects the heart from I/R injury.

A cardiac-specific and tamoxifen-inducible MAO-B knockout mouse (MAO-B KO) was generated using the Cre/lox system; Cre-negative MAO-B-fl/fl littermates served as controls (WT). Lack of MAO-B was verified by Western blot and immunohistochemistry. Cardiac function of MAO-B KO and WT was analyzed by echocardiography, quantification of mitochondrial ROS production, and measurement of myocardial infarct size (in % of ventricle) in hearts exposed to global I/R using the Langendorff technique. MAO-B protein expression was significantly down-regulated in MAO-B KO mice after two weeks of tamoxifen feeding followed by ten weeks of feeding with normal chow. ROS formation stimulated by the MAO-B-specific substrate beta-phenylethylamin (PEA; 250 mu M) was significantly lower in mitochondria isolated from MAO-B KO compared to WT hearts (WT 4.5 +/- 0.8 a. u.; MAO-B KO 1.2 +/- 0.3 a. u.). Echocardiography revealed no significant differences in LV dimensions as well as ejection fraction (EF) between WT and MAO-B KO mice (EF: WT 67.3 +/- 8.8%; MAO-B KO 67.7 +/- 6.5%). After I/R, infarct size was significantly lower in MAO-B KO hearts (WT 69.3 +/- 15.1%; MAO-B KO 46.8 +/- 12.0%).

Conclusion: Lack of cardiomyocytes-specific MAO-B reduces infarct size suggesting that MAO-B activity contributes to acute reperfusion injury.

Harvard Citation style: Heger, J., Hirschhaeuser, C., Bornbaum, J., Sydykov, A., Dempfle, A., Schneider, A., et al. (2021) Cardiomyocytes-specific deletion of monoamine oxidase B reduces irreversible myocardial ischemia/reperfusion injury, Free Radical Biology and Medicine, 165, pp. 14-23. https://doi.org/10.1016/j.freeradbiomed.2021.01.020

APA Citation style: Heger, J., Hirschhaeuser, C., Bornbaum, J., Sydykov, A., Dempfle, A., Schneider, A., Braun, T., Schlueter, K., & Schulz, R. (2021). Cardiomyocytes-specific deletion of monoamine oxidase B reduces irreversible myocardial ischemia/reperfusion injury. Free Radical Biology and Medicine. 165, 14-23. https://doi.org/10.1016/j.freeradbiomed.2021.01.020