Deficiency of nitric oxide synthase 2 results in increased neointima formation in a mouse model of vascular injury

Sirsjö, AllanKarolinska Institute, Sweden; University of Örebro, Sweden (author)

Restenosis frequently occurs after arterial interventions. The inducible form of nitric oxide synthase (NOS2) may both promote and inhibit neointima formation. This study investigated the role of NOS2 for neointima formation in a mouse model of carotid artery injury. The common carotid artery was ligated in anesthetized mice. Homozygous NOS2 knockout mice were compared with wild-type B6/129 mice or wild-type mice treated with the pharmacologic NOS2 inhibitor aminoguanidine given orally daily after ligation (n = 6-8 in each group). Vessels were harvested for quantification of lesion size 4 weeks later, or serially after ligation for tissue analysis. mRNA for NOS2 increased 1-4 days after ligation of the carotid artery. Cell proliferation could be visualized with an antibody against proliferating cell nuclear antigen. An intimal smooth muscle cell layer, confirmed by an alpha-actin antibody, was observed in the lumen 4 weeks after injury. Inhibition of NOS2 by either pharmacologic or genetic approaches tended to increase the area of intima formation (P = 0.13 or P less than 0.05, respectively) and increased the intima/media ratio (P = 0.14 and P less than 0.01, respectively). Inhibition of NOS2 by two different approaches increased neointima formation in a mouse model of mechanical vessel injury, indicating that the NOS2 expressed in the injured vessel wall is beneficial.

Löfving, AndersKarolinska Institute, Sweden (author)
Hansson, Göran K.Karolinska Institutet (author)
Wågsäter, DickKarolinska Institute, Sweden; University of Örebro, Sweden(Swepub:liu)dicwa60 (author)
Tokuno, S.Karolinska Institute, Sweden (author)
Valen, G.Karolinska Institute, Sweden (author)
Karolinska Institute, Sweden; University of Örebro, SwedenKarolinska Institute, Sweden (creator_code:org_t)

In:Journal of Cardiovascular Pharmacology: Lippincott Williams & Wilkins41:6, s. 897-9020160-24461533-4023

By the author/editor: Sirsjö, Allan; Löfving, Anders; Hansson, Göran K ...; Wågsäter, Dick; Tokuno, S.; Valen, G.

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