Localized adenovirus-mediated gene transfer into vascular smooth muscle in the hamster cheek pouch

Mary D. Frame, Joseph M. Miano, Jay Yang, Richard J. Rivers

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Objective: Our purpose was to develop a method for adenovirus delivery to the hamster cheek pouch to experimentally target gene transfer in tissue used for microvascular studies. Methods: Separate constructs were tested with transgenes for lacZ or green fluorescent protein (GFP) driven by three promoters: RSV, CMV, and SM22. With university approval, adenovirus was delivered in anesthetized (pentobarbital, 70 mg/kg) hamsters (n = 28) by using either a vascular systemic injection or tissue infiltration (interstitial space behind the pouch). During 3 days, animals receiving infiltration gained the expected weight, whereas those receiving vascular injection lost weight; no other behavior changes were noted. Results: On day 3 postadenoviral delivery (infiltration), expression of lacZ (histology, β-galactosidase) or GFP (fluorescence microscopy) was confirmed across the tissue (CMV and RSV promoters) and exclusively in vascular smooth muscle cells (specific SM22 promoter), without evidence of tissue inflammation. In vitro microvascular experiments verified normal responses in the cheek pouch of day 3 postadenoviral delivery animals. We tested local dilation to methacholine, adenosine, remote dilation to methacholine, adenosine, nitroprusside, and LM609 (αvβ3 integrin agonist), flow-dependent dilation, and flow recruitment. Conclusions: Thus, this method enables targeted, cell-specific gene transfer to one tissue important for microvascular studies, without significant systemic, exposure and without adverse inflammation.

Original languageEnglish (US)
Pages (from-to)403-413
Number of pages11
JournalMicrocirculation
Volume8
Issue number6
DOIs
StatePublished - Dec 1 2001
Externally publishedYes

Keywords

  • Adenovirus
  • Microcirculation
  • Non-invasive delivery
  • Promoter
  • Smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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