JACC: Basic to Translational Science (Feb 2019)

miR-29b Mediates the Chronic Inflammatory Response in Radiotherapy-Induced Vascular Disease

  • Suzanne M. Eken, MD, PhD,
  • Tinna Christersdottir, MD,
  • Greg Winski, MD,
  • Traimate Sangsuwan, MSc,
  • Hong Jin, MD, PhD,
  • Ekaterina Chernogubova, PhD,
  • John Pirault, PhD,
  • Changyan Sun, MSc,
  • Nancy Simon, MSc,
  • Hanna Winter, MSc,
  • Alexandra Backlund, PhD,
  • Siamak Haghdoost, PhD,
  • Göran K. Hansson, MD, PhD,
  • Martin Halle, MD, PhD,
  • Lars Maegdefessel, MD, PhD

Journal volume & issue
Vol. 4, no. 1
pp. 72 – 82

Abstract

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Summary: As a consequence of the success of present-day cancer treatment, radiotherapy-induced vascular disease is emerging. This disease is caused by chronic inflammatory activation and is likely orchestrated in part by microRNAs. In irradiated versus nonirradiated conduit arteries from patients receiving microvascular free tissue transfer reconstructions, irradiation resulted in down-regulation of miR-29b and up-regulation of miR-146b. miR-29b affected inflammation and adverse wound healing through its targets pentraxin-3 and dipeptidyl-peptidase 4. In vitro and in vivo, we showed that miR-29b overexpression therapy, through inhibition of pentraxin-3 and dipeptidyl-peptidase 4, could dampen the vascular inflammatory response. Key Words: arteriosclerosis, inflammation, microRNA, radiotherapy