title: Chronic infusion of salusin-alpha and -beta exerts opposite effects on atherosclerotic lesion development in apolipoprotein E-deficient mice.
abstract: OBJECTIVE
  Human salusin-alpha and -beta are two-related peptides processed from the same precursor, preprosalusin. Our previous in vitro studies have shown that human macrophage foam cell formation is stimulated by salusin-beta but suppressed by salusin-alpha. Thus we investigated the effects of salusin-alpha and -beta on atherosclerotic plaque formation in vivo in apolipoprotein E-deficient (ApoE-/-) mice.
  
  
  METHODS
  Saline (vehicle), salusin-alpha or -beta (0.6 nmol/kg/h) was continuously infused through osmotic mini-pumps into 13-week-old ApoE-/- mice for 8 weeks. Aortic atherosclerosis, oxidized LDL-induced cholesterol ester accumulation (foam cell formation), and its related gene expression in exudate peritoneal macrophages were determined.
  
  
  RESULTS
  After 4-week infusion of salusin-beta, atherosclerotic lesions were 2.6 times greater than vehicle controls, which paralleled 1.9-fold increase in foam cell formation and up-regulation of scavenger receptors (CD36, scavenger receptor class A) and acyl-CoA: cholesterol acyltransferase-1 (ACAT1). In contrast, salusin-alpha decreased serum total cholesterol levels by 15% and foam cell formation by 68% associated with ACAT1 down-regulation. After 8-week infusion of salusin-alpha, atherosclerotic lesions were significantly suppressed by 54% compared with vehicle controls.
  
  
  CONCLUSIONS
  Our study provided the first evidence that salusin-beta accelerates the development of atherosclerotic lesions associated with up-regulation of scavenger receptors and ACAT1 in ApoE-/- mice. Whilst, salusin-alpha exerts anti-atherosclerotic effects by suppressing serum total cholesterol levels and ACAT1 expression.
authors.affiliation: Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, Showa University School of Medicine, Tokyo 142-8666, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nagashima
authors.forename: Takuya
authors.initials: T
authors.lastname: Watanabe
authors.forename: Yuji
authors.initials: Y
authors.lastname: Shiraishi
authors.forename: Ryou
authors.initials: R
authors.lastname: Morita
authors.forename: Michishige
authors.initials: M
authors.lastname: Terasaki
authors.forename: Shigeko
authors.initials: S
authors.lastname: Arita
authors.forename: Shigeki
authors.initials: S
authors.lastname: Hongo
authors.forename: Kengo
authors.initials: K
authors.lastname: Sato
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Shichiri
authors.forename: Akira
authors.initials: A
authors.lastname: Miyazaki
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Hirano
mesh_terms: D000101:Acetyl-CoA C-Acetyltransferase / Q000378:metabolism; D000818:Animals; D001018:Aortic Diseases / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D001794:Blood Pressure; D001835:Body Weight; D018955:CD36 Antigens / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005487:Foam Cells / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D006339:Heart Rate; D006801:Humans; D015918:Infusion Pumps, Implantable; D055104:Infusions, Subcutaneous; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage* / Q000009:adverse effects*; D008077:Lipoproteins, LDL / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D051117:Scavenger Receptors, Class A / Q000378:metabolism; D013997:Time Factors
chemical_list: D001057:Apolipoproteins E; D018955:CD36 Antigens; D002788:Cholesterol Esters; D036341:Intercellular Signaling Peptides and Proteins; D008077:Lipoproteins, LDL; D051117:Scavenger Receptors, Class A; C478739:TOR2A protein, human; C099252:oxidized low density lipoprotein; D002784:Cholesterol; C506641:Acat1 protein, mouse; D000101:Acetyl-CoA C-Acetyltransferase