Transduction Efficiency of Adenovirus Vectors in Endothelial Cells and Vascular Smooth Muscle Cells

J Cardiovasc Pharmacol. 2020 Jun;75(6):603-607. doi: 10.1097/FJC.0000000000000821.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM17 Protein / genetics
  • ADAM17 Protein / metabolism
  • Adenoviridae / genetics*
  • Animals
  • Cells, Cultured
  • Coxsackie and Adenovirus Receptor-Like Membrane Protein / metabolism*
  • Endothelial Cells / metabolism*
  • Genetic Vectors*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Hexadimethrine Bromide / chemistry
  • Liposomes
  • Male
  • Mice, Inbred C57BL
  • Muscle, Smooth, Vascular / metabolism*
  • Myocytes, Smooth Muscle / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Angiotensin, Type 1 / genetics
  • Receptor, Angiotensin, Type 1 / metabolism
  • Transduction, Genetic*

Substances

  • CLMP protein, mouse
  • Clmp protein, rat
  • Coxsackie and Adenovirus Receptor-Like Membrane Protein
  • Liposomes
  • Receptor, Angiotensin, Type 1
  • Green Fluorescent Proteins
  • Hexadimethrine Bromide
  • ADAM17 Protein
  • Adam17 protein, mouse