TRIM21 deficiency alleviated MI-induced atrial oxidative damage, Cx43 downregulation, atrial fibrosis and enlargement, and electrocardiogram abnormalities in a mouse model.
Does TRIM21 deficiency prevent atrial remodeling and inflammation post-myocardial infarction in mice?
TRIM21 deficiency protects against post-MI atrial remodeling and inflammation by attenuating oxidative stress via the NF-κB/Nox2 pathway.
Atrial remodeling is a major contributor to the onset of atrial fibrillation (AF) after myocardial infarction (MI). Tripartite motif-containing protein 21 (TRIM21), an E3 ubiquitin protein ligase, is associated with pathological cardiac remodeling and dysfunction. However, the role of TRIM21 in postmyocardial infarction atrial remodeling and subsequent AF remains unclear. This study investigated the role of TRIM21 in post myocardial infarction atrial remodeling using TRIM21 knockout mice and explored the underlying mechanisms by overexpressing TRIM21 in HL-1 atrial myocytes using a lentiviral vector. The expression of TRIM21 in the left atrium of the mouse MI model was significantly elevated. TRIM21 deficiency alleviated MI-induced atrial oxidative damage, Cx43 downregulation, atrial fibrosis and enlargement, and abnormalities in electrocardiogram parameters (prolongation of the P-wave and PR interval). TRIM21 overexpression in atrial myocyte HL-1 cells further enhanced oxidative damage and Cx43 downregulation, whereas these effects were reversed by the reactive oxygen species scavenger N-acetylcysteine. The findings suggest that TRIM21 likely induces Nox2 expression mechanistically by activating the NF-κB pathway, which in turn leads to myocardial oxidative damage, inflammation, and atrial remodeling.
Liu et al. (Wed,) conducted a other in Post-myocardial infarction atrial remodeling. TRIM21 deficiency was evaluated on Atrial oxidative damage, Cx43 downregulation, atrial fibrosis and enlargement, and abnormalities in electrocardiogram parameters. TRIM21 deficiency alleviated MI-induced atrial oxidative damage, Cx43 downregulation, atrial fibrosis and enlargement, and electrocardiogram abnormalities in a mouse model.