doi: 10.1161/hq0901.095750
© 2001 American Heart Association, Inc.
Vascular Biology |
Experimental Abdominal Aortic Aneurysms in Mice Lacking Expression of Inducible Nitric Oxide Synthase
From the Departments of Surgery (Section of Vascular Surgery) (J.K.L., M.B., T.L.E., R.W.T), Radiology (R.W.T), and Cell Biology and Physiology (R.W.T.), Washington University School of Medicine, Saint Louis, Mo, and Department of Surgery (Section of Vascular Surgery) (G.R.U.), University of Michigan Medical School, Ann Arbor, Mich.
Correspondence to Robert W. Thompson, MD, Section of Vascular Surgery, Washington University School of Medicine, 9901 Wohl Hospital, 4960 Children’s Place, St. Louis, MO 63110. E-mail thompsonr{at}msnotes.wustl.edu
Abstract—— To determine if nitric oxide synthase (NOS) contributes to the pathophysiology of abdominal aortic aneurysms (AAAs), C57BL/6J mice underwent transient aortic injury to induce a chronic inflammatory response. Wild-type mice developed a significant increase in aortic diameter within 14 days of elastase perfusion (115±16%, 40% incidence of AAAs), along with intense and widespread staining for nitrotyrosine, mononuclear inflammation, and delayed destruction of the elastic lamellae. Expression of both endothelial and neuronal forms of NOS was substantially decreased within AAAs, whereas inducible NOS (iNOS) mRNA was increased 360%, and the enzyme was localized to infiltrating inflammatory cells. By using mice with targeted deletion of iNOS to evaluate the functional importance of this enzyme, male iNOS-/- mice developed the same extent of aneurysmal dilatation as congenic controls (121±22%, 40% incidence of AAAs) and exhibited similar structural features except for diminished nitrotyrosine staining. Aneurysmal dilatation was actually enhanced in female iNOS-/- mice (141±16%, 80% incidence of AAAs; P<0.05), but this effect was reversed by previous oophorectomy. Although extensive protein nitration and increased expression of iNOS accompany the development of elastase-induced experimental AAAs, iNOS is not required in this process and its absence may be deleterious.
Key Words: abdominal aortic aneurysm • animal model • elastase • inducible nitric oxide synthase • genetically altered mice
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