Cardiomyopathy commonly occurs after
sepsis and is closely associated with high mortality in clinic.
Interferon regulatory factor-2 binding protein 2 (IRF2BP2) has been identified as a negative regulator of
inflammation, but its role in septic
cardiomyopathy is unknown. The current study aims to illuminate the regulatory function of IRF2BP2 on
sepsis-induced
cardiomyopathy and to explore the underlying mechanisms.
Protein expression of IRF2BP2 in response to
sepsis-induced
cardiomyopathy was examined in the heart of mice challenged by LPS
intraperitoneal injection. AAV9-delivered IRF2BP2 overexpression in the heart was applied to evaluate the regulatory role of IRF2BP2 in
sepsis-induced myocardial depression, inflammatory response, and cell death. The molecular mechanisms underlying IRF2BP2-regulated
cardiomyopathy were explored using western blot screening assay. Primary cardiomyocytes have been isolated to further confirm the role and mechanism of IRF2BP2 during septic
cardiomyopathy. IRF2BP2 expression was dramatically increased in the heart of mice after LPS administration. AAV9-mediated IRF2BP2 overexpression significantly improved
sepsis-induced cardiac dysfunction, inhibited inflammatory cell infiltration and
cytokine production, and blocked cell death after LPS treatment. Mechanistically, IRF2BP2 activated AMPK signaling in cardiomyocytes, while inhibiting AMPK activation largely reversed IRF2BP2-benefited inflammatory suppression and cell survival. These findings clearly demonstrated that IRF2BP2 is a potent suppressor of
sepsis-induced myocardial depression and related heart impairment. Targeting IRF2BP2 represents a promising therapeutic strategy for septic
cardiomyopathy.