Cardamonin attenuates angiotensin II-induced abdominal aortic aneurysms through activation of the Nrf2/HO-1 pathway

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Background Cardamonin is a natural chalcone compound. It has been shown to have various pharmacological properties. Cardamonin can activate the Nrf2 signaling pathway. Abdominal aortic aneurysm (AAA) is a complex degenerative aortic disease. Ruptured AAAs continue to be among the leading causes of sudden death in elderly individuals. No medical therapy has proven clinical benefits for preventing AAA progression. Therefore, an adjunctive medical therapy is essential to address this unmet clinical need. Methods Human aortic smooth muscle cells (HASMCs) were used to determine the molecular mechanism of cardamonin. A murine model of angiotensin II (AngII)-induced AAA was used to assess the therapeutic effects of cardamonin on AAA growth in apolipoprotein E knockout (ApoE KO) mice in vivo . Immunoblotting, senescence assays, and reactive oxygen species (ROS) production assays were used to determine the protective effects of cardamonin in vivo and in vitro . Results Cardamonin induced Nrf2 translocation from the cytosol to the nuclear compartment in HASMCs. Cardamonin reduced AngII-induced ROS production and matrix metalloproteinases (MMPs) overexpression through activation of the Nrf2/heme oxygenase-1 (HO-1) antioxidant pathway in HASMCs. Silencing HO-1 attenuated the anti-ROS effects of cardamonin and abolished the protective effects of cardamonin in AngII-challenged HASMCs. Cardamonin (20 mg/kg/day) reduced AngII-induced AAA in vivo . Cardamonin also reduced the overexpression of MMPs and the production of ROS and attenuated elastin degradation in aortic tissues. Conclusion Cardamonin inhibits the progression of AngII-induced AAA through Nrf2/HO-1-mediated antioxidant and anti-inflammatory pathways. Cardamonin could have the potential to be an adjunctive therapy for small AAAs.

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