Isoproterenol induces MD2 activation by β-AR-cAMP-PKA-ROS signalling axis in cardiomyocytes and macrophages drives inflammatory heart failure.

ABSTRACT: Cardiac inflammation contributes to heart failure (HF) induced by isoproterenol (ISO) through activating β-adrenergic receptors (β-AR). Recent evidence shows that myeloid differentiation factor 2 (MD2), a key protein in endotoxin-induced inflammation, mediates inflammatory heart diseases. In this study, we investigated the role of MD2 in ISO-β-AR-induced heart injuries and HF. Mice were infused with ISO (30 mg·kg^-1·d^-1) via osmotic mini-pumps for 2 weeks. We showed that MD2 in cardiomyocytes and cardiac macrophages was significantly increased and activated in the heart tissues of ISO-challenged mice. Either MD2 knockout or administration of MD2 inhibitor L6H21 (10 mg/kg every 2 days, i.g.) could prevent mouse hearts from ISO-induced inflammation, remodelling and dysfu

SUBMITTER: Qian JF 

PROVIDER: S-EPMC10834947 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature