title: Anti-salusin-β antibody enhances angiogenesis after myocardial ischemia reperfusion injury.
abstract: BACKGROUND
  Salusins are multifunctional endogenous bioactive peptides simultaneously biosynthesized from their precursor prosalusin. Salusin-β stimulates proliferation of vascular smooth muscle cells and fibroblasts and regulates myocardial growth and hypertrophy. Salusin-β has potent hypotensive, bradycardic and proatherosclerotic effects.
  
  
  OBJECTIVE
  To investigate whether salusin-β plays a role in myocardial remodeling after myocardial ischemia reperfusion (I/R) injury, rat I/R models were created by the left anterior descending coronary artery occlusion for 30 min, followed by 24 h or 7 days of reperfusion (control, n = 6 each).
  
  
  CONCLUSIONS
  Immunohistochemical double staining showed the enhanced expression of salusin-β in the macrophages around myocardial ischemic area. Anti-salusin-β treated groups were administered the neutralizing salusin-β antibody (10 μl/day, i.p.) once daily from day -1 to day 1 or from day -1 to day 7 (anti-salusin-β, n = 6 each). The anti-salusin-β therapy enhanced myocardial angiogenesis in the peri-ischemic area of reperfusion. The small vessels (< 40 μm in diameter) of I/R hearts treated with anti-salusin-β were more densely populated than those of control animals (108.5 ± 19.7 vs 47.5 ± 2.4, p < 0.05). Real-time PCR revealed that the anti-salusin-β therapy-induced angiogenesis was not associated with enhanced vascular endothelial growth factor A expression. The authors, for the first time, have clarified that endogenous salusin-β suppresses angiogenesis which is critical in the development of cardiac remodeling following I/R injury.
authors.affiliation: Tokyo Medical and Dental University, Department of Cardiovascular Medicine , 1-5-45 Yushima, Bunkyo, Tokyo 113-8510 , Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Masumura
authors.forename: Ryo
authors.initials: R
authors.lastname: Watanabe
authors.forename: Ayako
authors.initials: A
authors.lastname: Nagashima
authors.forename: Masahito
authors.initials: M
authors.lastname: Ogawa
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Suzuki
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Shichiri
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Isobe
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology* / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D000906:Antibodies; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D042461:Vascular Endothelial Growth Factor A; C528274:salusin-beta, rat; C467498:vascular endothelial growth factor A, rat; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat