| Co-Investigator(Kenkyū-buntansha) |
ICHIMORI Kouji Tokai Univ., School of Medicine, Assistant Professor, 医学部, 講師 (60184636)
ISHIDA Hideyuki Tokai Univ., School of Medicine, Assistant Professor, 医学部, 講師 (20222424)
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| Research Abstract |
Chronic inhibition of nitric oxide (NO) production accelerates atherosclerosis, while enhanced production of NO suppresses the development of atherosclerosis or even regresses the lesions. These effects of NO largely depend on its antioxidant action. On the other hand, a high flux of NO from iNOS may favor formation of peroxynitrite and produce nitrotyrosine and functions as proatherogenic. Thus, the role of inducible NOS (iNOS) in the development of atherosclerosis remains to be established. We examined the susceptibility of iNOS^<-/-> and iNOS^<+/+> mice to the development of atherosclerosis induced by an atherogenic diet and analyzed the composition of the atherosclerotic lesions in the two strains to clarify the influence of iNOS on the atherogenesis.
Plasma lipid level, atherosclerotic lesion size and cellular density in the lesions were all similar in the two strains (lesion size : iNOS^<+/+> 285±73 vs. iNOS^<-/-> 293±82×10^3 μm^2, n=10). iNOS mRNA was detected in the lesions of iNOS^<+/+> but not iNOS^<-/-> mice by a reverse transcriptase-polymerase chain reaction (RT-PCR) method. Immunohistochemically, iNOS^<+/+> 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 iNOS^<-/-> mice. There was no apparent difference in the intensity or distribution of VCAM-1 staining in the lesions of the two strains. However, the lesions of iNOS^<+/+> mice showed a markedly decreased extracellular collagen content compared with those of iNOS^<-/-> mice
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.
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