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. 2022 Jun 27;12(11):5034–5050. doi: 10.7150/thno.75121

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Protective mechanism of DAPA on cardiac microvascular ischemia reperfusion injury. DAPA reduced XO expression and activity and inhibited reperfusion-mediated SERCA2 oxidation and inactivation. SERCA2 stabilization inhibited intracellular calcium overload and thus prevented CaMKII-mediated cofilin phosphorylation, resulting in preserved cytoskeleton integrity and decreased endothelial apoptosis. These beneficial effects of DAPA contribute to improved microvascular integrity in the presence of cardiac ischemia reperfusion (I/R) injury.