Key result
Adenoviruses effectively transduced aortic endothelial cells due to abundant CAR expression, whereas cationic liposomes enhanced transduction efficiency in vascular smooth muscle cells lacking CAR.
Why the study?
Differences in adenoviral transduction efficiencies, cationic liposome sensitivity, and CAR expression between endothelial cells and vascular smooth muscle cells were not fully understood.
Adenoviruses effectively transduce aortic ECs due to abundant CAR expression, whereas cationic liposomes enhance transduction efficiency in VSMCs lacking CAR expression.
May inform vector selection in preclinical vascular gene therapy; leaves open human translation.
Adenoviral vectors are useful tools in manipulating a gene of interest in vitro and in vivo, including in the vascular system. The transduction efficiencies of adenoviral vectors in vascular cells such as endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are known to be lower than those in epithelial cell types. The effective entry for adenoviral vectors is primarily mediated through the coxsackievirus and adenovirus receptor (CAR), which has been shown to be expressed in both cell types. Cationic liposomes have been used to enhance adenovirus transduction efficiency in nonepithelial cells. Accordingly, the aim of this study is to obtain new information regarding differences in transduction efficiencies, cationic liposome sensitivity, and CAR expression between ECs and VSMCs. Using cultured rat aortic ECs and VSMCs, here, we have compared transduction efficiency of adenoviruses with or without inclusion of liposomes and CAR expression. A significant increase in basal transduction efficiency was observed in ECs compared with VSMCs. Cationic liposome polybrene enhanced transduction efficiency in VSMCs, whereas decreased efficiency was observed in ECs. Western blotting demonstrated expression of the CAR in ECs but not in VSMCs. Proteomic analysis and mouse aorta immunostaining further suggests significant expression of the CAR in ECs but not in VSMCs. In conclusion, adenoviruses can effectively transduce the gene of interest in aortic ECs likely because of abundant expression of the CAR, whereas cationic liposomes such as polybrene enhance the transduction efficiency in VSMCs lacking CAR expression.
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Mokhashi et al. (2020) studied this question. Adenoviral vectors with or without cationic liposomes vs. Endothelial cells vs vascular smooth muscle cells was evaluated on Transduction efficiency and CAR expression. Adenoviruses effectively transduced aortic endothelial cells due to abundant CAR expression, whereas cationic liposomes enhanced transduction efficiency in vascular smooth muscle cells lacking CAR.
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