Atheroprotective Effects of Neuronal Nitric Oxide Synthase in Apolipoprotein E Knockout Mice

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Abstract
Objective— All 3 isoforms of the nitric oxide synthase (NOS) are expressed in atherosclerotic lesions. To test whether neuronal NOS (nNOS) deficiency affects atherosclerosis, we studied apoE/nNOSα double knockout (DKO) and apolipoprotein E (apoE) knockout (KO) control mice. Methods and Results— Lesion area was significantly increased in male DKO (66%) mice after 14 weeks and in female DKO animals (31%) after 24 weeks of “western” diet. Moreover, mean arterial blood pressure was significantly reduced in female DKO animals. Immunohistochemistry revealed nNOS expression in the neointima of KO mice. In DKO animals, residual nNOS staining was caused by the presence of nNOS splice variants. Whereas nNOSα was present in vessels of KO and absent in DKO animals, nNOSγ was expressed in KO and DKO mice. Conclusion— nNOSα protects against atherosclerosis as nNOSα deletion leads to an increase in plaque formation in apoE/nNOSα DKO mice. Female DKO mice showed a significant reduction in mean arterial blood pressure. Ad... Here we test whether neuronal NOS (nNOS) deficiency affects atherosclerosis in apoE/nNOSα double knockout (DKO) and apoE knockout animals. Male and female DKO animals showed a significant increase in lesion-area. Thus, nNOSα protects against atherosclerosis. Female but not male DKO mice showed a significant reduction in mean arterial blood pressure.