Inhibition of development of experimental abdominal aortic aneurysm by c-jun N-terminal protein kinase inhibitor combined with lysyl oxidase gene modified smooth muscle progenitor cells

Eur J Pharmacol. 2015 Nov 5:766:114-21. doi: 10.1016/j.ejphar.2015.09.046. Epub 2015 Oct 3.

Abstract

Chronic inflammation, imbalance between the extracellular matrix synthesis and degradation, and loss of vascular smooth muscle cells (SMCs) contribute to the development of abdominal aortic aneurysm (AAA). The purpose of this study was to investigate the effect of the therapy with periaortic incubation of c-Jun N-terminal protein kinase inhibitor SP600125 infused from an osmotic pump and subadventitial injection of lysyl oxidase (LOX) gene modified autologous smooth muscle progenitor cells (SPCs) on treatment of AAA in a rabbit model. Obvious dilation of the abdominal aorta in the control group was caused by periaortic incubation of calcium chloride and elastase. But the progression of aortic dilation was significantly decreased after the treatment with SP600125 and LOX gene modified SPCs compared to the treatment with phosphate-buffered saline. This therapy could inhibit matrix metalloproteinases expression, enhance elastin synthesis, improve preservation of elastic laminar integrity, benefit SPCs survival and restore SMCs population. It seemed that this method might provide a novel therapeutic strategy to treat AAA.

Keywords: Abdominal aortic aneurysm; C-Jun N-terminal protein kinase; Drug delivery system; SP600125; SP600125 (PubChem CID: 8515); Smooth muscle progenitor cell.

MeSH terms

  • Animals
  • Anthracenes / pharmacology
  • Anthracenes / therapeutic use*
  • Aorta, Abdominal / diagnostic imaging
  • Aorta, Abdominal / physiopathology
  • Aortic Aneurysm, Abdominal / diagnostic imaging
  • Aortic Aneurysm, Abdominal / physiopathology
  • Aortic Aneurysm, Abdominal / therapy*
  • Combined Modality Therapy
  • Humans
  • Leukocytes, Mononuclear
  • Male
  • Myocytes, Smooth Muscle / cytology
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Lysine 6-Oxidase / genetics*
  • Protein-Lysine 6-Oxidase / metabolism
  • Rabbits
  • Stem Cell Transplantation*
  • Stem Cells
  • Ultrasonography

Substances

  • Anthracenes
  • Protein Kinase Inhibitors
  • pyrazolanthrone
  • Protein-Lysine 6-Oxidase