title: Senescence marker protein-30 deficiency impairs angiogenesis under ischemia.
abstract: Aging decreases collateral-dependent flow recovery following acute arterial obstruction. However, the mechanisms are partially understood, therefore critical management has been lacked in clinical setting. Senescence marker protein-30 (SMP30) is a novel aging marker, which is assumed to act as an anti-aging factor in various organs. Therefore, we studied the effect of SMP30 on ischemia-induced collateral growth in SMP30 knockout (KO) mice, young and old C57BL/6 mice. The SMP30 expression in gastrocnemius tissue was decreased in old mice compared to that of young mice. The recovery of cutaneous blood flow in hind limb after femoral artery ligation and tissue capillary density recoveries were suppressed in SMP30 KO and old mice compared to those in young mice. Nitric oxide generation induced by l-arginine and GSH/GSSG in aorta of SMP30 KO and old mice were lower than those in young mice. The levels of NADPH oxidase activity and superoxide production in the ischemic tissue were higher in SMP30 KO and old mice than in young mice. The phosphorylated eNOS and Akt levels and VEGF levels in ischemic muscle were lower in SMP30 KO and old mice than in young mice. Deficiency of SMP30 exacerbates oxidative stress related to NADPH oxidase activity enhancement and impairs eNOS activity, which leads to rarefaction of angiogenesis induced by ischemia. These results suggest that SMP30 plays a key role in disrupting collateral growth under ischemia in aging.
authors.affiliation: Department of Cardiology and Hematology, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamauchi
authors.affiliation: Department of Cardiology and Hematology, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Miura
authors.affiliation: Department of Cardiology and Hematology, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Owada
authors.affiliation: Department of Cardiology and Hematology, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan. Electronic address: sais@fmu.ac.jp.
authors.forename: Shu-Ichi
authors.initials: S
authors.lastname: Saitoh
authors.affiliation: Department of Cardiology and Hematology, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Machii
authors.affiliation: Department of Cardiology and Hematology, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Ishigami
authors.affiliation: Department of Cardiology and Hematology, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan.
authors.forename: Yasuchika
authors.initials: Y
authors.lastname: Takeishi
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001120:Arginine / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D007511:Ischemia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics; D010766:Phosphorylation; D017382:Reactive Oxygen Species; D013481:Superoxides / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017382:Reactive Oxygen Species; C513324:Rgn protein, mouse; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D013481:Superoxides; D009569:Nitric Oxide; D001120:Arginine; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D051058:Oncogene Protein v-akt; D005978:Glutathione
keywords: Angiogenesis; Ischemia; Nitric oxide; Oxidative stress; Senescence marker protein-30 (SMP30)