In vivo suppression of injury-induced vascular smooth muscle cell accumulation using adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene. Academic Article uri icon

Overview

MeSH

  • Adenoviridae
  • Angioplasty, Balloon
  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Carotid Stenosis
  • Cell Division
  • Cells, Cultured
  • Coronary Disease
  • DNA Primers
  • DNA, Viral
  • Genetic Therapy
  • Humans
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Rats
  • Recurrence
  • Transfection
  • Virus Replication

MeSH Major

  • Aorta, Thoracic
  • Ganciclovir
  • Muscle, Smooth, Vascular
  • Simplexvirus
  • Thymidine Kinase

abstract

  • Restenosis, a process characterized in part by excessive smooth muscle cell (SMC) proliferation in areas of vascular injury, occurs in up to 50% of patients undergoing balloon angioplasty. In an effort to develop a treatment strategy for restenosis, we constructed a replication-deficient recombinant adenovirus (AdMLP.HSTK) containing the herpes simplex virus thymidine kinase gene (HSV tk). This viral gene product phosphorylates the prodrug ganciclovir to form a nucleoside analog that inhibits DNA synthesis. Cultured primary rat SMCs infected with AdMLP.HSTK were completely growth-inhibited by incubation in ganciclovir-containing medium. In addition, when only a portion of the SMC population received the HSV tk transgene, an inhibitory effect on neighboring SMCs was evident. Evaluation of this strategy in vivo using a rat carotid balloon injury model demonstrated that local infection of injured arteries with AdMLP.-HSTK followed by 2 weeks of systemic ganciclovir treatment significantly (P < 0.01) reduced injury-induced SMC accumulation. In contrast, there was no suppression of injury-induced SMC accumulation in animals infected with AdMLP.HSTK but not receiving ganciclovir or in those animals infected with a control adenovirus and either treated or not treated with ganciclovir. These results demonstrate the potential utility of adenovirus-mediated gene transfer for treatment of restenosis after balloon injury.

publication date

  • October 25, 1994

has subject area

  • Adenoviridae
  • Angioplasty, Balloon
  • Animals
  • Animals, Genetically Modified
  • Aorta, Thoracic
  • Base Sequence
  • Carotid Stenosis
  • Cell Division
  • Cells, Cultured
  • Coronary Disease
  • DNA Primers
  • DNA, Viral
  • Ganciclovir
  • Genetic Therapy
  • Humans
  • Molecular Sequence Data
  • Muscle, Smooth, Vascular
  • Polymerase Chain Reaction
  • Rats
  • Recurrence
  • Simplexvirus
  • Thymidine Kinase
  • Transfection
  • Virus Replication

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC45096

PubMed ID

  • 7938020

Additional Document Info

start page

  • 10732

end page

  • 10736

volume

  • 91

number

  • 22