Inducible Nitric Oxide Synthase Deficiency Does Not Affect the Susceptibility of Mice to Atherosclerosis but Increases Collagen Content in Lesions

Background—Although endothelial nitric oxide synthase (NOS) is antiatherogenic, the role of inducible NOS (iNOS) in the development of atherosclerosis is not established. Methods and Results—We compared the susceptibility of iNOS knockout (iNOS2/2) and wild-type (iNOS1/1) mice to the development of atherosclerosis induced by feeding an atherogenic diet for 15 weeks. Plasma lipid level, atherosclerotic lesion size, and cellular density in the lesions were all similar in the 2 strains (lesion size: iNOS1/1 2856733103 mm2, iNOS2/2 2936823103 mm2, n510). iNOS mRNA was detected in the lesions of iNOS1/1 but not iNOS2/2 mice through RT-PCR. Immunohistochemically, iNOS1/1 mice showed iNOS staining in macrophages and medial smooth muscle cells in the lesions. Nitrotyrosine staining showed a similar distribution, whereas it was absent in iNOS2/2 mice. There was no apparent difference in the intensity or distribution of vascular cell adhesion molecule-1 staining in the lesions of the 2 strains. However, the lesions of iNOS1/1 mice showed a markedly decreased extracellular collagen content compared with those of iNOS2/2 mice Conclusions—iNOS induction does not affect the development of atherosclerosis in mice fed an atherogenic diet, but the resulting lesions show decreased levels of extracellular collagen and may be more fragile. (Circulation. 2001;103:1115-1120.) Key Words: mice, inbred n atherosclerosis n nitric oxide synthas