title: Atherosclerotic lesions are associated with increased immunoreactivity for inducible nitric oxide synthase and endothelin-1 in thoracic aortic intimal cells of hyperlipidemic Watanabe rabbits.
abstract: The development and progression of atherosclerotic lesions in Watanabe heritable hyperlipidemic rabbits is associated with increases in inducible nitric oxide synthase (NOS2) and endothelin-1 (ET-1) immunoreactivity. In contrast, there is a reduction of immunoreactivity for neuronal NOS (NOS1) in aortic endothelial cells, but no change in endothelial NOS (NOS3) immunoreactivity. However, subendothelial macrophages and smooth muscle showed a different pattern of immunoreactivity of NADPH-diaphorase (NADPH-d), NOS2, ET-1, and NOS1. The lipid-rich macrophages in the intima were positively labeled for NADPH-d, NOS1, NOS2, NOS3, and ET-1. Smooth muscle cells in the subendothelium and the medial layers of the vascular wall were also positive for these markers. These results are consistent with the reduction of endothelium-dependent vasorelaxation that is known to occur during the development and progression of atherosclerosis in familial hypercholesterolemia. The data suggest a key role for vasoactive substances in the development of atherosclerosis.
authors.affiliation: Laboratory of Electron Microscopy, Department of Neurology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106-4938, USA.
authors.forename: G
authors.initials: G
authors.lastname: Aliev
authors.forename: M A
authors.initials: MA
authors.lastname: Smith
authors.forename: M
authors.initials: M
authors.lastname: Turmaine
authors.forename: M L
authors.initials: ML
authors.lastname: Neal
authors.forename: T V
authors.initials: TV
authors.lastname: Zimina
authors.forename: R P
authors.initials: RP
authors.lastname: Friedland
authors.forename: G
authors.initials: G
authors.lastname: Perry
authors.forename: J C
authors.initials: JC
authors.lastname: LaManna
authors.forename: G
authors.initials: G
authors.lastname: Burnstock
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001013:Aorta, Thoracic / Q000254:growth & development / Q000473:pathology / Q000502:physiology*; D001161:Arteriosclerosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D003593:Cytoplasm / Q000378:metabolism / Q000648:ultrastructure; D008058:Dihydrolipoamide Dehydrogenase / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure; D019332:Endothelin-1 / Q000032:analysis / Q000502:physiology*; D006949:Hyperlipidemias / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D008264:Macrophages / Q000502:physiology; D008297:Male; D016253:Microscopy, Immunoelectron; D008931:Mitochondria, Muscle / Q000378:metabolism / Q000648:ultrastructure; D024510:Muscle Development; D009131:Muscle, Smooth, Vascular / Q000254:growth & development / Q000473:pathology / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D011817:Rabbits; D017539:Tunica Intima / Q000254:growth & development / Q000473:pathology / Q000502:physiology*
chemical_list: D019332:Endothelin-1; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D008058:Dihydrolipoamide Dehydrogenase