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 ≈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.