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 antiatheroge nic, the role of inducible NOS (iNOS) in the development: of atherosclerosi s is not established. Methods and Results-We compared the susceptibility of iNOS knockout (iNOS(- /-)) and wild-type (iNOS(+/+)) mice to the development of atherosclerosis i nduced by feeding an atherogenic diet for 15 weeks. Plasma lipid level, ath erosclerotic lesion size, and cellular density in the lesions were all simi lar in the 2 strains (lesion size: iNOS(+/+) 285+/-73x10(3) mum(2), iNOS(-/ -) 293+/-82x10(3) mum(2), n=10). iNOS mRNA was detected in the lesions of i NOS(+/+) but not iNOS(-/-) mice through RT-PCR. Immunohistochemically, iNOS (+/+) mice showed iNOS staining in macrophages and medial smooth muscle cel ls in the lesions. Nitrotyrosine staining showed a similar distribution, wh ereas it was absent in iNOS(-/-) mice. There was no apparent difference in the intensity or distribution of vascular eel adhesion molecule-1 staining in the lesions of the 2 strains. However, the lesions of iNOS(+/+) mice sho wed a markedly decreased extracellular collagen content compared with those of iNOS(-/-) mice. Conclusions-iNOS induction does not affect the development of atheroscleros is in mice fed an atherogenic diet, but the resulting lesions show decrease d levels of extracellular collagen and may be more fragile.