Abstract 259: Insulin Growth Factor 1 Gene Therapy Protects Against Iugr Induced Elevation in Blood Pressure by Restoring Renal Architecture

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Compelling epidemiological and clinical evidence has identified a specific nephropathy in growth restricted offspring (IUGR), characterized by elevated blood pressure and adverse renal structural remodelling. We demonstrated that intraplacental gene transfer of adenoviral insulin growth factor1 (AdIGF1) corrects reduced birth weight and elevated blood pressure in a mouse model of placental insufficiency. We hypothesized that AdIGF1 protects against IUGR induced adult onset hypertension by restoring renal architecture

Method Laparotomy was performed on pregnant C57BL/6J at E18. Pups were divided into: Sham operated; IUGR: by selective ligation of uterine artery; IUGR+IGF1: intra placental AdIGF1 after ligation (N=9). Pups delivered on E20, blood pressure was measured biweekly. At 32 weeks, kidney of the offsprings were histologically processed and whole mounted. After every 20 section, a 5 um consecutive primary and reference sections were stained with H&E. Physical fractionator probe in stereo investigator analysed nephron count, mean glomerular diameter & area. Data analysed using ANOVA

Result IUGR significantly reduced nephron count vs SHAM and IUGR+IGF1 (1688 ± 36 vs 1997 ± 27 vs 1899 ± 75, p=0.05), increased mean glomerular diameter (90.7 ± 2.8 vs 67.3 ± 2.9 vs 68.5 ± 4.3, p<0.001), increased total glomerular area (1.2x107 vs 7.6x106 vs 8.3x106, p<0.05)

Discusion Intraplacental AdIGF1 restored IUGR induced alteration in renal architecture. Elevated blood pressure and glomerular hypertrophy may indicate a compensatory mechanism for reduction of nephron count. This demonstrate a novel therapeutic approach for reprogramming and early targeting of hypertension

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