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Publication - Professor Costanza Emanueli

    Nerve Growth Factor Gene Therapy using Adeno-Associated Viral Vectors Prevents Cardiomyopathy in Type 1 Diabetic Mice

    Citation

    Meloni, M, Descamps, B, Caporali, A, Zentilin, L, Floris, I, Giacca, M & Emanueli, C 2012, ‘Nerve Growth Factor Gene Therapy using Adeno-Associated Viral Vectors Prevents Cardiomyopathy in Type 1 Diabetic Mice’. Diabetes, vol 61., pp. 229 - 240

    Abstract

    Objective: Diabetes is cause of cardiac dysfunction, reduced myocardial perfusion and ultimately
    heart failure. Nerve growth factor (NGF) exerts protective effects on the cardiovascular system.
    This study investigated if NGF gene therapy can prevent diabetic cardiomyopathy in mice.
    Research design and methods: Type 1 diabetes mellitus was induced in CD1 male mice by
    streptozotocin. Non-diabetic age-matched control male mice received the streptozotocin buffer.
    Murine NGF mRNA expression in the heart was measured by real-time RT-PCR at 12 weeks of
    diabetes. At 2 weeks of diabetes, cardiac expression of human NGF or β-Gal genes was induced
    by either intra-myocardial injection of adeno-associated virus vectors serotype 2 (AAV2) or
    systemic injection of AAV9. Non-diabetic mice received AAV2-β-Gal or AAV9-β-Gal.
    Results: Diabetes lowered the cardiac expression of endogenous NGF mRNA. A progressive
    deterioration of cardiac function and left ventricular chamber dilatation appeared in β-Gal–treated
    diabetic mice. At 12 weeks of diabetes, β-Gal–treated mice showed myocardial microvascular
    rarefaction, hypoperfusion, more interstitial fibrosis and increased apoptosis of endothelial cells
    and cardiomyocytes. NGF gene therapy using either AAV2 or AAV9 prevented diabetes-induced
    cardiac dysfunction, reduced cardiac apoptosis and preserved cardiac microvasculature and blood
    flow.
    Conclusions: AAV vectors-mediated myocardial NGF overexpression can prevent diabetesinduced
    cardiac dysfunction and myocardial microangiopathy. These results suggest the
    therapeutic potential of NGF for the prevention of cardiomyopathy in diabetic subjects.

    Full details in the University publications repository