title: Adiponectin association with T-cadherin protects against neointima proliferation and atherosclerosis.
abstract: Adiponectin, an adipocyte-derived protein abundant in the circulation, is thought to be protective against atherosclerosis. However, it is not fully understood how the association of adiponectin with vascular cells and its antiatherogenic effect are connected. In this study, T-cadherin was essential for accumulation of adiponectin in the neointima and atherosclerotic plaque lesions, and the adiponectin-T-cadherin association protected against vascular injury. In the apolipoprotein E-knockout (ApoE-KO) mice, adiponectin and T-cadherin colocalized on endothelial cells and synthetic smooth muscle cells in the aortic intima. Notably, aortic adiponectin protein disappeared in T-cadherin/ApoE double-knockout (Tcad/ApoE-DKO) mice with significant elevation of blood adiponectin concentration. Furthermore, in Tcad/ApoE-DKO mice, carotid artery ligation resulted in a significant increase of neointimal thickness compared with ApoE-KO mice. Finally, on a high-cholesterol diet, Tcad/ApoE-DKO mice increased atherosclerotic plaque formation, despite a 5-fold increase in plasma adiponectin level compared with that in ApoE-KO mice.In vitro, knockdown of T-cadherin from human aortic smooth muscle cells (HASMCs) with synthetic phenotype significantly reduced adiponectin accumulation on HASMCs and negated the inhibitory effect of adiponectin on proinflammatory change. Collective evidence showed that adiponectin accumulates in the vasculatureviaT-cadherin, and the adiponectin-T-cadherin association plays a protective role against neointimal and atherosclerotic plaque formations.-Fujishima, Y., Maeda, N., Matsuda, K., Masuda, S., Mori, T., Fukuda, S., Sekimoto, R., Yamaoka, M., Obata, Y., Kita, S., Nishizawa, H., Funahashi, T., Ranscht, B., Shimomura, I. Adiponectin association with T-cadherin protects against neointima proliferation and atherosclerosis.
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Fujishima
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan; norikazu_maeda@endmet.med.osaka-u.ac.jp.|Department of Metabolism and Atherosclerosis, Graduate School of Medicine, Osaka University, Osaka, Japan; and.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Maeda
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Matsuda
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Masuda
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Mori
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Fukuda
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Sekimoto
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Yamaoka
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Obata
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.|Department of Metabolism and Atherosclerosis, Graduate School of Medicine, Osaka University, Osaka, Japan; and.
authors.forename: Shunbun
authors.initials: S
authors.lastname: Kita
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nishizawa
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.|Department of Metabolism and Atherosclerosis, Graduate School of Medicine, Osaka University, Osaka, Japan; and.
authors.forename: Tohru
authors.initials: T
authors.lastname: Funahashi
authors.affiliation: Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ranscht
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
mesh_terms: D052242:Adiponectin / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology
chemical_list: D052242:Adiponectin; D015820:Cadherins; C099972:H-cadherin
keywords: cardiovascular diseases; inflammation; metabolic syndrome; obesity; smooth muscle cells