TRIM55 Aggravates Cardiomyocyte Apoptosis After Myocardial Infarction via Modulation of the Nrf2/HO-1 Pathway

• Published in: JACC. Basic to translational science 2024-09, Vol.9 (9), p.1104-1122
• Main Authors: Bu, Yuxin, Liu, Yanxia, Liu, Meili, Yan, Chenghui, Wang, Jing, Wu, Hanlin, Song, Haixu, Zhang, Dali, Xu, Kai, Liu, Dan, Han, Yaling
• Format: Article
• Language: English
• Subjects: apoptosis; HO-1; myocardial infarction; Nrf2; Original Research - Preclinical; Trim55
• ISSN: 2452-302X; 2452-302X
• DOI: 10.1016/j.jacbts.2024.05.006

[Display omitted] •Trim55 knockout improved cardiac dysfunction and cardiomyocyte apoptosis after MI, whereas overexpression aggravated cardiac dysfunction after MI.•Trim55 regulated cardiomyocyte apoptosis by inhibiting the Nrf2/HO-1 pathway.•Trim55 regulated the Nrf2/HO-1 pathway by interacting with Nrf2.•Trim55 was regulated by the transcription factor Foxo3 under hypoxia. Tripartite motif-containing 55 (Trim55) is mainly expressed in myocardium and skeletal muscle, which plays an important role in promoting the embryonic development of the mouse heart. We investigated the role of Trim55 in myocardial infarction and the associated molecular mechanisms. We studied both gain and loss of function in vivo and in vitro. The results showed that Trim55 knockout improved cardiac function and apoptosis after myocardial infarction, and overexpression aggravated cardiac function damage. The mechanism is that Trim55 interacts with nuclear factor, erythroid derived 2 (Nrf2) to accelerate its degradation and inhibit the expression of heme oxygenase 1, thereby promoting cardiomyocyte apoptosis.