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Monoamine oxidase-A (MAO-A), a key enzyme involved in catecholamine metabolism and longstanding antidepressant target, is highly expressed in the myocardium. The present study aimed to elucidate the functional significance and underlying mechanisms of cardiac MAO-A in arrhythmogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Analysis of the TriNetX database revealed that depressed patients treated with MAO inhibitors had a lower risk of arrhythmias compared with those treated with selective serotonin reuptake inhibitors. This effect was phenocopied in mice with cardiomyocyte-specific MAO-A deficiency (cMAO-Adef), which showed a significant reduction in both incidence and duration of catecholamine stress-induced ventricular tachycardia compared with wild-type mice. Additionally, cMAO-Adef cardiomyocytes exhibited altered Ca2+ handling under catecholamine stimulation, with increased diastolic Ca2+ reuptake, reduced diastolic Ca2+ leak, and diminished systolic Ca2+ release. Mechanistically, cMAO-Adef hearts had reduced catecholamine levels under sympathetic stress, along with reduced levels of reactive oxygen species and protein carbonylation, leading to decreased oxidation of Type II PKA and CaMKII. These changes potentiated phospholamban (PLB) phosphorylation, thereby enhancing diastolic Ca2+ reuptake, while reducing ryanodine receptor 2 (RyR2) phosphorylation to decrease diastolic Ca2+ leak. Consequently, cMAO-Adef hearts exhibited lower diastolic Ca2+ levels and fewer arrhythmogenic Ca2+ waves during sympathetic overstimulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Cardiac MAO-A inhibition exerts an anti-arrhythmic effect by enhancing diastolic Ca2+ handling under catecholamine stress.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvae012","type":"journal-article","created":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T02:17:36Z","timestamp":1704853056000},"page":"596-611","source":"Crossref","is-referenced-by-count":18,"title":["Cardiac monoamine oxidase-A inhibition protects against catecholamine-induced ventricular arrhythmias via enhanced diastolic calcium 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,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Streeter","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Carver College of Medicine, University of Iowa , 285 Newton Rd, Iowa City, IA 52242 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Carver College of Medicine, University of Iowa , 285 Newton Rd, Iowa City, IA 52242 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Huo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa , 180 S Grand Ave., Iowa City, IA 52242 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean C","family":"Shih","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California , 1985 Zonal Avenue, Los Angeles, CA 90089 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biyi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Carver College of Medicine, University of Iowa , 285 Newton Rd, Iowa City, IA 52242 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duane","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Carver College of Medicine, University of Iowa , 285 Newton Rd, Iowa City, IA 52242 ,","place":["USA"]},{"name":"Abboud Cardiovascular Research Center, Carver College of Medicine, University of Iowa , CBRB 2267285, Newton Rd, Iowa City, IA 52242 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E Dale","family":"Abel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Carver College of Medicine, University of Iowa , 285 Newton Rd, Iowa City, IA 52242 ,","place":["USA"]},{"name":"Abboud Cardiovascular Research Center, Carver College of Medicine, University of Iowa , CBRB 2267285, Newton Rd, Iowa City, IA 52242 ,","place":["USA"]},{"name":"Fraternal Order of Eagles Diabetes Research Center, Carver College of Medicine, University of Iowa , 169 Newton Rd, Iowa City, IA 52242 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6035-8106","authenticated-orcid":false,"given":"Long-Sheng","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Carver College of Medicine, University of Iowa , 285 Newton Rd, Iowa City, IA 52242 ,","place":["USA"]},{"name":"Abboud 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