title: Adipokine resistin is a key player to modulate monocytes, endothelial cells, and smooth muscle cells, leading to progression of atherosclerosis in rabbit carotid artery.
abstract: OBJECTIVE
  We investigated the effects of human resistin on atherosclerotic progression and clarified its underlying mechanisms.
  
  
  BACKGROUND
  Resistin is an adipokine first identified as a mediator of insulin resistance in murine obesity models. But, its role in human pathology is under debate. Although a few recent studies suggested the relationship between resistin and atherosclerosis in humans, the causal relationship and underlying mechanism have not been clarified.
  
  
  METHODS
  We cloned rabbit resistin, which showed 78% identity to human resistin at the complementary deoxyribonucleic acid level, and its expression was examined in 3 different atherosclerotic rabbit models. To evaluate direct role of resistin on atherosclerosis, collared rabbit carotid arteries were used. Histological and cell biologic analyses were performed.
  
  
  RESULTS
  Rabbit resistin was expressed by macrophages of the plaque in the 3 different atherosclerotic models. Peri-adventitial resistin gene transfer induced macrophage infiltration and expression of various inflammatory cytokines, resulting in the acceleration of plaque growth and destabilization. In vitro experiments elucidated that resistin increased monocyte-endothelial cell adhesion by upregulating very late antigen-4 on monocytes and their counterpart vascular cell adhesion molecule-1 on endothelial cells. Resistin augmented monocyte infiltration in collagen by direct chemoattractive effect as well as by enhancing migration toward monocyte chemotactic protein-1. Administration of connecting segment-1 peptide, which blocks very late antigen-4 × vascular cell adhesion molecule-1 interaction, ameliorated neointimal growth induced by resistin in vivo.
  
  
  CONCLUSIONS
  Our results indicate that resistin aggravates atherosclerosis by stimulating monocytes, endothelial cells, and vascular smooth muscle cells to induce vascular inflammation. These findings provide the first insight on the causal relationship between resistin and atherosclerosis.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Youngjin
authors.initials: Y
authors.lastname: Cho
authors.forename: Sang-Eun
authors.initials: SE
authors.lastname: Lee
authors.forename: Hyun-Chae
authors.initials: HC
authors.lastname: Lee
authors.forename: Jin
authors.initials: J
authors.lastname: Hur
authors.forename: Sahmin
authors.initials: S
authors.lastname: Lee
authors.forename: Seock-Won
authors.initials: SW
authors.lastname: Youn
authors.forename: Jaewon
authors.initials: J
authors.lastname: Lee
authors.forename: Ho-Jae
authors.initials: HJ
authors.lastname: Lee
authors.forename: Tae-Kyu
authors.initials: TK
authors.lastname: Lee
authors.forename: Jonghanne
authors.initials: J
authors.lastname: Park
authors.forename: Seok-Jae
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Yoo-Wook
authors.initials: YW
authors.lastname: Kwon
authors.forename: Hyun-Jai
authors.initials: HJ
authors.lastname: Cho
authors.forename: Byung-Hee
authors.initials: BH
authors.lastname: Oh
authors.forename: Young-Bae
authors.initials: YB
authors.lastname: Park
authors.forename: Hyo-Soo
authors.initials: HS
authors.lastname: Kim
mesh_terms: D054392:Adipokines / Q000378:metabolism*; D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002340:Carotid Artery Diseases / Q000378:metabolism* / Q000473:pathology; D017536:Carotid Artery, Common / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018450:Disease Progression; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D011817:Rabbits; D052243:Resistin / Q000096:biosynthesis*
chemical_list: D054392:Adipokines; D052243:Resistin