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

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 ( ins2(Akita)) and leptin receptor db/ db ( lepr(db/ db)) mutant mice. Neointima size in ins2(Akita) mouse arteries was unchanged compared with nondiabetic wild- type littermates. Although Ki67 labeling demonstrated similar rates of replication in the neointima of lepr(db/ db) mouse arteries, neointimal formation in lepr(db/ db) mice was surprisingly reduced by approximate to 90% compared with nondiabetic lepr(+/+) mice. Four hours after arterial injury, medial smooth muscle cell death was diminished in lepr(db/ db) arteries, suggesting that the initial response to arterial injury was altered in lepr(db/ db) mice. Conclusions - These studies highlight a differential response to arterial injury in lepr(db/ db) mice and suggest a potential role for leptin in the regulation of neointimal formation in response to arterial injury.