title: Deficiency of senescence marker protein 30 exacerbates angiotensin II-induced cardiac remodelling.
abstract: OBJECTIVE
  Ageing is an important risk factor of cardiovascular diseases including heart failure. Senescence marker protein 30 (SMP30), which was originally identified as an important ageing marker protein, is assumed to act as a novel anti-ageing factor in various organs. However, the role of SMP30 in the heart has not been previously explored. In this study, our aim was to elucidate the functional role of SMP30 on cardiac remodelling.
  
  
  RESULTS
  SMP30 knockout (KO) mice and wild-type (WT) mice were subjected to continuous angiotensin II (Ang II) infusion. After 14 days, the extent of cardiac hypertrophy and myocardial fibrosis was significantly higher in SMP30-KO mice than in WT mice. Echocardiography revealed that SMP30-KO mice had more severely depressed systolic and diastolic function with left ventricular dilatation compared with WT mice. Generation of reactive oxygen species related with activation of nicotinamide adenine dinucleotide phosphate-oxidase was greater in SMP30-KO mice than in WT mice. The number of deoxynucleotidyl transferase-mediated dUTP nick end-labelling positive nuclei was markedly increased in SMP30-KO mice with activation of caspase-3, increases in the Bax to Bcl-2 ratio and phosphorylation of c-Jun N-terminal kinase compared with WT mice. Furthermore, the number of senescence-associated β-galactosidase-positive cells was significantly increased via up-regulation of p21 gene expression in SMP30-KO mice compared with WT mice.
  
  
  CONCLUSIONS
  This study demonstrated the first evidence that deficiency of SMP30 exacerbates Ang II-induced cardiac hypertrophy, dysfunction, and remodelling, suggesting that SMP30 has a cardio-protective role in cardiac remodelling with anti-oxidative and anti-apoptotic effects in response to Ang II.
authors.affiliation: Department of Cardiology and Hematology, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan.
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Misaka
authors.forename: Satoshi
authors.initials: S
authors.lastname: Suzuki
authors.forename: Makiko
authors.initials: M
authors.lastname: Miyata
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kobayashi
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Shishido
authors.forename: Akihito
authors.initials: A
authors.lastname: Ishigami
authors.forename: Shu-ichi
authors.initials: S
authors.lastname: Saitoh
authors.forename: Masamichi
authors.initials: M
authors.lastname: Hirose
authors.forename: Isao
authors.initials: I
authors.lastname: Kubota
authors.forename: Yasuchika
authors.initials: Y
authors.lastname: Takeishi
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000804:Angiotensin II / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D001205:Ascorbic Acid / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D006333:Heart Failure / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction; D020257:Ventricular Remodeling / Q000502:physiology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494827:Bax protein, mouse; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C513324:Rgn protein, mouse; D051028:bcl-2-Associated X Protein; D000804:Angiotensin II; C052617:Bcl2 protein, mouse; C505409:Casp3 protein, mouse; D053148:Caspase 3; D001205:Ascorbic Acid
keywords: Ageing; Apoptosis; Oxidative stress; Remodelling; Senescence marker protein 30 (SMP30)