Abstract 13662: Intra-Placental Gene Transfer of Human Insulin-Like Growth Factor-1 Rescues Postnatal Intra-Uterine Growth Restriction Induced Cardiac Dysfunction
Objective Intrauterine growth restriction (IUGR), defined as birth weight <10% for gestational age, is a risk factor for adult onset cardiovascular diseases, which may be characterized by impaired ventricular function. We have shown that intra-placental adenoviral mediated gene transfer of human insulin-like growth factor 1(Ad hIGF1) corrects birth weight in a new surgical mouse model of IUGR, but the potential benefit of this therapy on associated cardiac dysfunctions is unknown. We hypothesized that intra-placental Ad hIGF1 would restore in vivo postnatal cardiac function in a mouse model of IUGR. Study Design Laparotomy was performed on pregnant C57BL/6J mice at embryonic day 18 and pups were divided into 3 groups.
Control: Sham operated; IUGR: surgically induced by ligation of a branch of mesenteric uterine artery; IGF1Treated: intra placental injection of Ad hIGF1 after ligation. Pups were delivered on day 20, cross fostered to surrogate CD1 mice, sorted by gender at 4 weeks, and evaluated at 12 weeks. Cross-sectional, 2D, M-mode and Doppler transthoracic echocardiography was performed evaluating ejection fraction (EF), fractional shortening (FS), and left ventricular (LV) dimensions. Data were analyzed using Chi-square or ANOVA.
Results. IUGR mice demonstrated significantly reduced EF (40 ± 10.1 vs. 59.8 ± 4.2 vs. 58.6 ± 5.3, p < 0.001, n = 12) and FS (19.9 ± 4.4 vs. 31.3 ± 5.1 vs. 32.2 ± 5.3, p < 0.001,n = 12) compared to SHAM which was normalized in the treatment group (Figure A). IUGR significantly increased LVID;S (3.8± 0.3 vs 3.1± 0.49 vs 2.9 ± 0.4 p<0.001, n=12) as compared to SHAM and restored to normal in IGF1 Treated (Figure B). These findings were the same when data was stratified by sex. Conclusion Intra-placental gene transfer of Ad hIGF1 rescues IUGR-induced cardiac dysfunction. This supports the concept that in utero therapy may positively impact cardiac remodeling to attenuate fetal cardiovascular dysfunction and prevent adult onset cardiovascular disease.
- © 2012 by American Heart Association, Inc.