title: The roles of salusins in atherosclerosis and related cardiovascular diseases.
abstract: Human salusin-α and -β are related peptides of 28 and 20 amino acids, respectively, produced from the same precursor, prosalusin. Salusin-β exerts more potent mitogenic effects on human vascular smooth muscle cells (VSMCs) and fibroblasts than salusin-α. Human macrophage foam cell formation is significantly stimulated by salusin-β, but suppressed by salusin-α. Chronic salusin-β infusion into apolipoprotein E-knockout mice enhances atherosclerotic lesions, paralleling increases in foam cell formation and upregulation of scavenger receptors and of acyl-CoA:cholesterol acyltransferase-1 (ACAT1) in macrophages. In contrast, chronic salusin-α infusion reduces atherosclerotic lesions accompanied by significant suppression of foam cell formation owing to ACAT1 downregulation. Salusin-β is expressed in proliferative neointimal lesions of porcine coronary arteries after stenting. Salusin-α and -β immunoreactivity has been detected in human coronary atherosclerotic plaques, with dominance of salusin-β in macrophage foam cells, VSMCs, and fibroblasts. Serum salusin-α levels are markedly decreased in patients with angiographically proven coronary artery disease compared with patients with mild hypertension and healthy volunteers. Furthermore, among patients with acute coronary syndrome, serum salusin-α levels are decreased in accordance with the severity of coronary atherosclerotic lesions. These findings suggest that salusin-β may contribute to the pathogenesis of atherosclerosis. Decreased levels of salusin-α in circulating blood and vascular tissue are closely linked with human atherosclerosis. Therefore, salusin-α could be a candidate biomarker for atherosclerosis and may be therapeutically useful for prevention of atherosclerotic cardiovascular diseases.
authors.affiliation: Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan. watanabe@toyaku.ac.jp
authors.forename: Takuya
authors.initials: T
authors.lastname: Watanabe
authors.forename: Kengo
authors.initials: K
authors.lastname: Sato
authors.forename: Fumiko
authors.initials: F
authors.lastname: Itoh
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Iso
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nagashima
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Hirano
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Shichiri
mesh_terms: D000101:Acetyl-CoA C-Acetyltransferase / Q000097:blood / Q000502:physiology; D000818:Animals; D050197:Atherosclerosis / Q000503:physiopathology*; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D058426:Neointima / Q000378:metabolism / Q000473:pathology
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C478739:TOR2A protein, human; C506639:ACAT1 protein, human; D000101:Acetyl-CoA C-Acetyltransferase