Epigenetic upregulation of endogenous VEGF-A reduces myocardial infarct size in mice.
“Epigenetherapy” alters epigenetic status of the targeted chromatin and modifies expression of the endogenous therapeutic gene. In this study we used lentiviral in vivo delivery of small hairpin RNA (shRNA) into hearts in a murine infarction model. shRNA complementary to the promoter of vascular endothelial growth factor (VEGF-A) was able to upregulate endogenous VEGF-A expression. Histological and multiphoton microscope analysis confirmed the therapeutic effect in the transduced hearts. Magnetic resonance imaging (MRI) showed in vivo that the infarct size was significantly reduced in the treatment group 14 days after the epigenetherapy. Importantly, we show that promoter-targeted shRNA upr…
Elevated end systolic function in a rat model of temporal lobe epilepsy
Sudden unexpected death in epilepsy (SUDEP) is a common cause of premature death amongst epilepsy patients. It is hypothesized to result from cardiorespiratory dysfunction, but the exact aetiology is unknown. The aim of this study was to determine if functional cardiovascular alterations were present in rats with chronic epileptic behaviour. Naive control rats were compared to a rat model of temporal lobe epilepsy that was induced using a repeated low-dose kainic acid (KA) protocol. The results indicate that end-systolic volume was significantly (p=0.01) higher in the epileptic group whilst end-diastolic volume did not reach significance (p=0.08). Ejection fraction, stroke volume, cardiac o…
Magnetic resonance imaging of viral particle biodistribution in vivo
We describe here a technique for the visualization of viral vector delivery by magnetic resonance imaging (MRI) in vivo. By conjugating avidin-coated baculoviral vectors (Baavi) with biotinylated ultra-small superparamagnetic iron oxide particles (USPIO), we are able to produce vector-related MRI contrast in the choroid plexus cells of rat brain in vivo over a period of 14 days. Ten microlitres of 2.5 x 10(10) PFU/ml nuclear-targeted LacZ-encoding Baavi with bUSPIO coating was injected into rat brain ventricles and visualized by MRI at 4.7 T. As baculoviruses exhibit restricted cell-type specificity in the rat brain, altered MRI contrast was detected in the choroid plexus of the injected ve…