Hui‑Chen Kua, Ta‑Chung Shenb, Ching‑Feng Chenga,c,d*
aDepartment of Pediatrics, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan, bDivision of Cardiovascular Surgery, Department of Surgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan, cInstitute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, dSchool of Medicine, Tzu Chi University, Hualien, Taiwan
Open Access funded by Buddhist Compassion Relief Tzu Chi Foundation
Abstract
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.
Keywords: Activating transcription factor 3, Inflammation, Itaconate, Nuclear factor erythroid 2‑related factor 2, Succinate dehydrogenase
