title: Contrasting effects of stanniocalcin-related polypeptides on macrophage foam cell formation and vascular smooth muscle cell migration.
abstract: Stanniocalcin (STC) is a calcium- and phosphate-regulating hormone secreted by the corpuscles of Stannius, an endocrine gland of bony fish. Its human homologues, STC1 and STC2 showing 34% amino acid identity each other, are expressed in a variety of human tissues. To clarify their roles in atherosclerosis, we investigated the effects of their full-length proteins, STC1(18-247) and STC2(25-302), and STC2-derived fragment peptides, STC2(80-100) and STC2(85-99), on inflammatory responses in human umbilical vein endothelial cells (HUVECs), human macrophage foam cell formation, the migration and proliferation of human aortic smooth muscle cells (HASMCs) and the extracellular matrix expression. All these polypeptides suppressed lipopolysaccharide-induced expressions of interleukin-6, monocyte chemotactic protein-1, and intercellular adhesion molecule-1 in HUVECs. Oxidized low-density lipoprotein-induced foam cell formation was significantly decreased by STC1(18-247) and increased by STC2(80-100) and STC2(85-99), but not STC2(25-302), in human macrophages. Expression of acyl-CoA:cholesterol acyltransferase-1 (ACAT1) was significantly suppressed by STC1(18-247) but stimulated by STC2(80-100) and STC2(85-99). Expression of ATP-binding cassette transporter A1 was significantly stimulated by STC1(18-247). Neither STC1(18-247) nor STC2-derived peptides significantly affected CD36 expression in human macrophages or HASMC proliferation. STC2(80-100) and STC2(85-99) significantly increased HASMC migration, whereas STC1(18-247) significantly suppressed the angiotensin II-induced HASMC migration. Expressions of collagen-1, fibronectin, matrix metalloproteinase-2, and elastin were mostly unchanged with the exception of fibronectin up-regulation by STC2(80-100). Our results demonstrated the contrasting effects of STC1 and STC2-derived peptides on human macrophage foam cell formation associated with ACAT1 expression and on HASMC migration. Thus, STC-related polypeptides could serve as a novel therapeutic target for atherosclerosis.
authors.affiliation: Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Tajima
authors.affiliation: Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Hasegawa
authors.affiliation: Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
authors.forename: Yui
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Kojima
authors.affiliation: Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
authors.forename: Rena
authors.initials: R
authors.lastname: Watanabe
authors.affiliation: Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Sato
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Shichiri
authors.affiliation: Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan. Electronic address: watanabe@toyaku.ac.jp.
authors.forename: Takuya
authors.initials: T
authors.lastname: Watanabe
mesh_terms: D000101:Acetyl-CoA C-Acetyltransferase / Q000235:genetics*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D005487:Foam Cells / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000008:administration & dosage* / Q000737:chemistry; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage* / Q000737:chemistry; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D010455:Peptides; C114997:STC2 protein, human; C051795:teleocalcin; C506639:ACAT1 protein, human; D000101:Acetyl-CoA C-Acetyltransferase
keywords: Atherosclerosis; Endothelial cell; Macrophage; Smooth muscle; Stanniocalcin-1; Stanniocalcin-2