Immunoproteasome Subunit β5i Promotes Ang II (Angiotensin II)–Induced Atrial Fibrillation by Targeting ATRAP (Ang II Type I Receptor–Associated Protein) Degradation in Mice

Atrial fibrillation (AF) is the most common type of cardiac arrhythmia and increases the risk of stroke, heart failure, and death. Ang II (angiotensin II) triggers AF, mainly through stimulation of the AT1R (Ang II type I receptor). The immunoproteasome is a highly efficient proteolytic machine derived from the constitutive proteasome, but the role it plays in regulating AT1R activation and triggering AF remains unknown. Here, we show that among the catalytic subunits, β5i (PSMB8) expression, and chymotrypsin-like activity were the most significantly upregulated in atrial tissue of Ang II–infused mice or serum from patients with AF. β5i KO (β5i knockout) in mice markedly attenuated Ang II-induced AF incidence, atrial fibrosis, inflammatory response, and oxidative stress compared with WT (wild type) animals, but injection with recombinant adeno-associated virus serotype 9–β5i increased these effects. Moreover, we found that ATRAP (AT1R-associated protein) was a target of β5i. Overexpression of ATRAP signif...