Abstract
BackgroundOur study aimed to demonstrate the feasibility of using the sodium/iodide symporter (NIS) to monitor vascular endothelial growth factor (VEGF165) expression in vivo.MethodsWe constructed a recombinant lentivirus plasmid with the MLC-2v promoter driving the sodium/iodide symporter (NIS) reporter gene linked to the VEGF165 gene. Expression of NIS and VEGF gene were identified by Western blot. On days 2 and 54, 99mTc-MIBI imaging was used to evaluate changes in myocardial ischemia. Noninvasive 125I micro-SPECT/CT imaging was used to assess the expression of NIS reporter gene dynamically over the next 2 months.ResultsWestern blot analysis showed that both NIS and VEGF165 were highly expressed in rat cardiomyoblast H9C2 cells transduced with Lenti-MLC-2v-NIS--VEGF165. 125I micro-SPECT/CT reporter imaging showed higher uptake in mouse myocardium transduced with Lenti-MLC-2v-VEGF165-IRES-NIS. NIS expression peaked on day 1 after transduction followed by a progressive decline to negligible levels by day 21. On day 1, mean 125I activity value in group 1 was higher than that in group 2 (P<0.05). The mean 125I activity value in group 3 was statically lower than that in group 1 and 2 (P<0.01). On day 60, 125I uptakes in test and positive control groups became very low, and no significant differences in the mean 125I activity values were detected between group 1 and group 2 (P = 0.531 > 0.05). In group 1 (test group), 99mTc-MIBI SPECT/CT revealed improvements in perfusion and wall thickening in the apical anterior wall. Mean IOD values of NIS and CD34 were significantly higher in group 1 than group 3 (P<0.05). Our study proved mean I-125 uptake was significantly correlated with mean IOD value of NIS and CD34 (P<0.05).ConclusionThis study demonstrates the feasibility of using the NIS gene to monitor VEGF165 expression in a mouse myocardial ischemia model.
Highlights
Ischemic heart disease (IHD) is the leading cause of death worldwide [1,2]
Our study aimed to demonstrate the feasibility of using the sodium/iodide symporter (NIS) to monitor vascular endothelial growth factor (VEGF165) expression in vivo
Western blot analysis showed that both NIS and VEGF165 were highly expressed in rat cardiomyoblast H9C2 cells transduced with Lenti-MLC-2v-NIS–VEGF165. 125I micro-SPECT/ CT reporter imaging showed higher uptake in mouse myocardium transduced with LentiMLC-2v-VEGF165-IRES-NIS
Summary
Ischemic heart disease (IHD) is the leading cause of death worldwide [1,2]. Patients with ischemic HF continue to experience unacceptably high rates of morbidity and mortality. Gene therapy for cardiovascular disease has great potential for a variety of application, but the lack of reliable monitoring methods has limited its development. Recent studies using the HSV1-tk reporter gene to monitor gene or stem cells in myocardial infarction model show encouraging results [9, 10]. Sodium/iodide symporter (NIS) is another promising imaging reporter gene [11]. Previous reports demonstrated the feasibility of using NIS for myocardial gene expression imaging in rats [12,13,14]. Few reports have investigated the combination of NIS with therapeutic genes in myocardial ischemia in vivo. Our study aimed to demonstrate the feasibility of using the sodium/iodide symporter (NIS) to monitor vascular endothelial growth factor (VEGF165) expression in vivo
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