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The potential of using itaconate as treatment for inflammation-related heart diseases
Hui-Chen Ku1, Ta-Chung Shen2, Ching-Feng Cheng3
1 Department of Pediatrics, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan
2 Division of Cardiovascular Surgery, Department of Surgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan
3 Department of Pediatrics, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei; Institute of Biomedical Sciences, Academia Sinica, Taipei; School of Medicine, Tzu Chi University, Hualien, Taiwan
Correspondence Address:
Ching-Feng Cheng
Department of Pediatrics, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 289, Jianguo Road, Xindian District, New Taipei
Taiwan
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/tcmj.tcmj_83_21
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Intracellular metabolites can cause critical changes in biological functions. Itaconate is perhaps the most fascinating substance in macrophages. Lipopolysaccharide can activate aconitate decarboxylase 1 and induces the generation of itaconate from the tricarboxylic acid cycle by decarboxylation of cis-aconitate. It has been reported that itaconate has beneficial effects on inflammation and oxidation. The mechanisms involved in these effects include the suppression of succinate dehydrogenase, the activation of nuclear factor E2-related factor 2 by alkylation of Kelch-like ECH-associated protein 1, suppression of aerobic glycolysis through regulation of glyceraldehyde-3-phosphate dehydrogenase and fructose-bisphosphate aldolase A, and suppression of IκBζ translation through activating transcription factor 3 activation. All of these findings elucidated the possible therapeutic implications of itaconate in inflammation-related diseases. In this review, we highlight that itaconate is a crucial molecule of the immunomodulatory response in macrophages and can regulate between immune response and cardiovascular metabolism. Furthermore, these discoveries suggest that itaconate is a very novel therapeutic molecule for the treatment of inflammation-related heart diseases.
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