Transcriptomic signature ofXPO1was highly expressed and inversely related to left ventricular function in ischemic cardiomy-opathy patients. We hypothesized that treatment with AAV9-shXPO1 attenuates left ventricular dysfunction and remodeling in amyocardial infarction rat model. We induced myocardial infarction by coronary ligation in Sprague-Dawley rats (n= 10), whichreceived AAV9-shXPO1 (n= 5) or placebo AAV9-scramble (n= 5) treatment. Serial echocardiographic assessment was per-formed throughout the study. After myocardial infarction, AAV9-shXPO1-treated rats showed partial recovery of left ventricularfractional shortening (16.8 ± 2.8 vs 24.6 ± 4.1%,P< 0.05) and a maintained left ventricular dimension (6.17 ± 0.95 vs 4.70 ±0.93 mm,P< 0.05), which was not observed in non-treated rats. Furthermore, lower levels of EXP-1 (P< 0.05) and lowercollagen fibers and fibrosis in cardiac tissue were observed. However, no differences were found in the IL-6 or TNFR1 plasmalevels of the myocardium of AAV9-shXPO1 rats. AAV9-shXPO1 administration attenuates cardiac dysfunction and remodelingin rats after myocardial infarction, producing the gene silencing ofXPO1.