Honokiol ameliorates angiotensin II‐induced cardiac hypertrophy by promoting dissociation of the Nur77–LKB1 complex and activating the AMPK pathway

Abstract

AbstractPathological cardiac hypertrophy is a key contributor to heart failure, and the molecular mechanisms underlying honokiol (HNK)‐mediated cardioprotection against this condition remain worth further exploring. This study aims to investigate the effect of HNK on angiotensin II (Ang II)‐induced myocardial hypertrophy and elucidate the underlying mechanisms. Sprague–Dawley rats were exposed to Ang II infusion, followed by HNK or vehicle treatment for 4 weeks. Our results showed that HNK treatment protected against Ang II‐induced myocardial hypertrophy, fibrosis and dysfunction in vivo and inhibited Ang II‐induced hypertrophy in neonatal rat ventricular myocytes in vitro. Mechanistically, HNK suppressed the Ang II‐induced Nur77 expression at the transcriptional level and promoted ubiquitination‐mediated degradation of Nur77, leading to dissociation of the Nur77–LKB1 complex. This facilitated the translocation of LKB1 into the cytoplasm and activated the LKB1‐AMPK pathway. Our findings suggest that HNK attenuates pathological remodelling and cardiac dysfunction induced by Ang II by promoting dissociation of the Nur77–LKB1 complex and subsequent activation of AMPK signalling. This study uncovers a novel role of HNK on the LKB1‐AMPK pathway to protect against cardiac hypertrophy.