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To establish the heart failure model, C57BL\/6NTac mice were given high\u2010dose isoproterenol (80\u2009mg\/kg body weight) for 14\u2009days. Echocardiography revealed that protocatechuic acid reversed the isoproterenol\u2010induced downregulation of fractional shortening and ejection fraction. Protocatechuic acid attenuated cardiac hypertrophy as evidenced by the decreased heart\u2010weight\u2010to\u2010body\u2010weight ratio and the expression of Nppb. RNA sequencing analysis identified kynurenine\u20103\u2010monooxygenase (Kmo) as a potential target of protocatechuic acid. Protocatechuic acid treatment or transfection with short\u2010interfering RNA against <jats:italic>Kmo<\/jats:italic> ameliorated transforming growth factor \u03b21\u2013induced upregulation of Kmo, Col1a1, Col1a2 and Fn1 in vivo or in neonatal rat cardiac fibroblasts. <jats:italic>Kmo<\/jats:italic> knockdown attenuated the isoproterenol\u2010induced increase in cardiomyocyte size, as well as Nppb and Col1a1 expression in H9c2 cells or primary neonatal rat cardiomyocytes. Moreover, protocatechuic acid attenuated Kmo overexpression\u2013induced increases in Nppb mRNA levels. Protocatechuic acid or <jats:italic>Kmo<\/jats:italic> knockdown decreased isoproterenol\u2010induced ROS generation in vivo and in vitro. Thus, protocatechuic acid prevents heart failure by downregulating Kmo. Therefore, protocatechuic acid and Kmo constitute a potential novel therapeutic agent and target, respectively, against heart failure.<\/jats:p>","DOI":"10.1111\/jcmm.17869","type":"journal-article","created":{"date-parts":[[2023,7,22]],"date-time":"2023-07-22T07:57:40Z","timestamp":1690012660000},"page":"2290-2307","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Protocatechuic acid prevents isoproterenol\u2010induced heart failure in mice by downregulating kynurenine\u20103\u2010monooxygenase"],"prefix":"10.1111","volume":"27","author":[{"given":"Liyan","family":"Bai","sequence":"first","affiliation":[{"name":"Heart Research Center of Chonnam National University Hospital  Gwangju Republic of Korea"},{"name":"Hypertension Heart Failure Research Center Chonnam National University Hospital  Gwangju Republic of Korea"},{"name":"Emergency Critical Center, Beijing Anzhen Hospital Capital Medical University  Beijing 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