title: Pathophysiological levels of the obesity related peptides resistin and ghrelin increase adhesion molecule expression on human vascular endothelial cells.
abstract: 1. In the present study, we sought to determine whether physiological or pathophysiological concentrations of obesity related peptides influence the key early atherogenic events of monocyte adhesion to endothelial cells and adhesion molecule expression using primary human cells. 2. Human umbilical vein endothelial cells were grown to confluence and human monocytes were obtained by elutriation. Adhesion was assessed by automated cell counting and cell adhesion molecule expression (E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)) was assayed by ELISA. 3. Experimental conditions included untreated control, ghrelin (100, 150, 450 and 1350 pmol/L), resistin (15, 40 and 100 ng/mL) and combined leptin and insulin (combinations of 30 and 120 pmol/L insulin and 5, 50 and 500 ng/mL leptin). 4. Both resistin and ghrelin produced modest but significant increases in VCAM-1 expression (110 +/- 4 and 117 +/- 13% compared with controls, respectively; both P <or= 0.01). Ghrelin also increased ICAM-1 expression (119 +/- 17% of control; P <or= 0.01). 5. However, despite these increases in adhesion molecule expression, neither ghrelin nor resistin altered monocyte adhesion values. 6. Neither leptin nor insulin altered monocyte adhesion to endothelial cells or cell adhesion molecule expression. 7. Pathophysiologically relevant concentrations of ghrelin and resistin, within the range of concentrations exhibited by patients with anorexia nervosa or the Prader-Willi syndrome and type 2 diabetes, respectively, increase endothelial cell adhesion molecule expression, possibly contributing to increased atherosclerosis risk in such subjects.
authors.affiliation: Department of Medicine, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Skilton
authors.forename: Shirley
authors.initials: S
authors.lastname: Nakhla
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Sieveking
authors.forename: Ian D
authors.initials: ID
authors.lastname: Caterson
authors.forename: David S
authors.initials: DS
authors.lastname: Celermajer
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000096:biosynthesis; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D054439:Ghrelin; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D020738:Leptin / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D036361:Peptide Hormones / Q000494:pharmacology*; D052243:Resistin / Q000494:pharmacology*; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D015815:Cell Adhesion Molecules; D019040:E-Selectin; D054439:Ghrelin; D007328:Insulin; D020738:Leptin; D036361:Peptide Hormones; D052243:Resistin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1