Protective effects of trehalose preconditioning on cardiac and coronary endothelial function through eNOS signaling pathway in a rat model of ischemia-reperfusion injury

Coronary endothelial dysfunction is a major cause of ischemia-reperfusion (I/R) injury. Trehalose, a natural disaccharide, has been reported to ameliorate endothelial dysfunction during aging by activating endothelial nitric oxide synthase (eNOS); however, its role in I/R injury is unknown. This study evaluated the effects of trehalose preconditioning on cardiac and coronary endothelial function after I/R. Langendorff-perfused rat hearts underwent 30 min of global ischemia followed by 80 min of reperfusion with or without trehalose preconditioning. Rate pressure product (RPP) and coronary flow (CF) were measured during reperfusion. Perivascular edema was assessed by hematoxylin and eosin staining. Myocardial oxidative stress and apoptosis were evaluated by immunohistochemistry and TUNEL staining, respectively. eNOS dimerization was determined by western blotting. An eNOS inhibitor was used to examine the role of eNOS. Trehalose preconditioning showed a higher recovery rate after I/R as indicated by high RPP (control vs. trehalose, 28 +/- 6% vs. 46 +/- 9%; P = 0.017, Cohen's d = 2.3) and CF values (35 +/- 10% vs. 55 +/- 9%; P = 0.025, d = 1.7). Furthermore, trehalose preconditioning reduced perivascular edema, myocardial oxidative stress, and apoptosis. The eNOS dimerization ratio was increased by trehalose (1.2 +/- 0.2 vs. 1.6 +/- 0.2; P = 0.023, d = 2.1), which was associated with the recovery of RPP and CF. These effects of trehalose were abolished by the eNOS inhibitor. Trehalose preconditioning showed protective effects on cardiac and coronary endothelial function after I/R through the eNOS signaling pathway.

Automated summary

This study evaluated the effects of trehalose preconditioning on cardiac and coronary endothelial function after ischemia-reperfusion injury. It was found that trehalose preconditioning improved heart function, reduced edema, oxidative stress, and apoptosis, and increased eNOS dimerization ratio, indicating its protective effects on cardiac and coronary endothelial function. These effects were mediated through the eNOS signaling pathway.