XPO1 Gene Therapy Attenuates Cardiac Dysfunction in Rats with Chronic Induced Myocardial Infarction

Figures

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  Fig. 1. Study protocol timeline. Baseline functional echocardiographic parameters were evaluated (stage 0) in rats before the experimental procedure. Functional parameters were studied in sham and LAD (left anterior descending) coronary artery ligation animals after procedure (stage I). Four months later, the animals were administered with either adeno-associated virus vector silencing XPO1 gene (AAV9-shXPO1) or placebo (AAV9-scramble) particles. After gene therapy, changes in functional parameters were evaluated by echocardiography 2 (stage II) and 5 (stage III) months later

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  Fig. 2. EXP-1 protein levels in AVV9-shXPO1 and AAV9-scramble rats. a Heart. b Skeletal muscle. c Liver. d Brain. The values are normalized to GAPDH, and then to the AAV9-scramble group. The values from the AAV9-scramble group were set to 100. The data are expressed as mean ± SEM in arbitrary units. Au, arbitrary units. *P < 0.05

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  Fig. 3. EXP-1 levels determined by immunoassay in infarcted AAV9-shXPO1 and AAV9-scrmable rats. Black bars, AVV9-scramble group; gray bars, AVV9-shXPO1 group. *P < 0.05

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  Fig. 4. Masson’s trichrome staining in sham (a), AAV9-scramble (b), and AAV9-shXPO1 (c) rat hearts. Detail of the ×10 sections of sham (d), AAV9-scramble (e), and AAV9-shXPO1 (f) rats. g Percentage of fibrotic areas in all groups of rats. Hematoxylin-eosin staining of sham (h), AAV9-scramble (i), and AAV9-shXPO1 (j) rats. ***P < 0.001 sham vs AAV9-scramble and AAV9-shXPO1; #P < 0.05 AAV9-scramble vs AAV9-shXPO1

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  Fig. 5. Echocardiographic parameters of infarcted AAV9-shXPO1 and AAV9-scramble rats measured before surgery and injection (stage 0), before injection (stage I), and 2 (stage II) and 5 months (stage III) after vector injection. a Fractional shortening. b Left ventricular end-systolic diameter. c Left ventricular end-diastolic diameter. ###P < 0.001 stage 0 vs stages 1, 2, and 3 in AAV9-scramble; ***P < 0.001 stage 0 vs stages 1 and 2 in AAV9-shXPO1; *P < 0.05 and **P < 0.01 stage 3 vs stages 1 and 2 in AAV9-shXPO1