Neointimal formation after endovascular arterial injury is markedly attenuated in db/db mice

Arterioscler Thromb Vasc Biol. 2003 Nov 1;23(11):2027-33. doi: 10.1161/01.ATV.0000096394.32433.E9. Epub 2003 Sep 18.

Abstract

Objective: A diabetic mouse model of accelerated neointimal formation would be a useful tool to understand the increased incidence of restenosis in patients with diabetes.

Methods and results: Femoral artery endoluminal wire injury was performed in diabetic insulin 2 Akita (ins2Akita) and leptin receptor db/db (leprdb/db) mutant mice. Neointima size in ins2Akita mouse arteries was unchanged compared with nondiabetic wild-type littermates. Although Ki67 labeling demonstrated similar rates of replication in the neointima of leprdb/db mouse arteries, neointimal formation in leprdb/db mice was surprisingly reduced by approximately 90% compared with nondiabetic lepr+/+ mice. Four hours after arterial injury, medial smooth muscle cell death was diminished in leprdb/db arteries, suggesting that the initial response to arterial injury was altered in leprdb/db mice.

Conclusions: These studies highlight a differential response to arterial injury in leprdb/db mice and suggest a potential role for leptin in the regulation of neointimal formation in response to arterial injury.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Coronary Restenosis / physiopathology
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Disease Models, Animal
  • Female
  • Femoral Artery / injuries
  • Femoral Artery / pathology
  • Femoral Artery / physiopathology
  • Leptin / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Muscle, Smooth, Vascular / injuries*
  • Muscle, Smooth, Vascular / pathology
  • Muscle, Smooth, Vascular / physiopathology
  • Neovascularization, Pathologic / physiopathology*
  • Sex Factors
  • Tunica Intima / pathology*
  • Tunica Intima / physiopathology*
  • Tunica Media / pathology

Substances

  • Leptin