title: The potential role of resistin in atherogenesis.
abstract: Resistin, an adipocyte-derived cytokine linked to insulin resistance and obesity, has recently been shown to activate endothelial cells (ECs). Using microarrays, we found that along with numerous other pro-atherosclerotic genes, resistin expression levels are elevated in the aortas of C57BL/6J apoE-/- mice; these findings led us to further explore the relation between resistin and atherosclerosis. Using TaqMan PCR and immunohistochemistry, we found that ApoE-/- mice had significantly higher resistin mRNA and protein levels in their aortas, and elevated serum resistin levels, compared to C57BL/6J wild-type mice. Incubation of murine aortic ECs with recombinant resistin increased monocyte chemoattractant protein (MCP)-1 and soluble vascular cell adhesion molecule (sVCAM)-1 protein levels in the conditioned medium. Furthermore, human carotid endarterectomy samples stained positive for resistin protein, while internal mammary artery did not show strong staining. Patients diagnosed with premature coronary artery disease (PCAD) were found to have higher serum levels of resistin than normal controls. In summary, resistin protein is present in both murine and human atherosclerotic lesions, and mRNA levels progressively increase in the aortas of mice developing atherosclerosis. Resistin induces increases in MCP-1 and sVCAM-1 expression in murine vascular endothelial cells, suggesting a possible mechanism by which resistin might contribute to atherogenesis. Finally, PCAD patients exhibited increased serum levels of resistin when compared to controls. These findings suggest a possible role of resistin in cardiovascular disease.
authors.affiliation: Cardiovascular Research Institute, MedStar Research Institute, Washington Hospital Center, 108 Irving Street, N.W., Room 217, Washington, DC 20010, USA. mary.s.burnett-miller@medstar.net
authors.forename: Mary Susan
authors.initials: MS
authors.lastname: Burnett
authors.forename: Cheol W
authors.initials: CW
authors.lastname: Lee
authors.forename: Tim D
authors.initials: TD
authors.lastname: Kinnaird
authors.forename: Eugenio
authors.initials: E
authors.lastname: Stabile
authors.forename: Sarfraz
authors.initials: S
authors.lastname: Durrani
authors.forename: Mercedes K
authors.initials: MK
authors.lastname: Dullum
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Devaney
authors.forename: Craig
authors.initials: C
authors.lastname: Fishman
authors.forename: Sotiris
authors.initials: S
authors.lastname: Stamou
authors.forename: Daniel
authors.initials: D
authors.lastname: Canos
authors.forename: Stephan
authors.initials: S
authors.lastname: Zbinden
authors.forename: Leonardo C
authors.initials: LC
authors.lastname: Clavijo
authors.forename: Gil Jin
authors.initials: GJ
authors.lastname: Jang
authors.forename: James A
authors.initials: JA
authors.lastname: Andrews
authors.forename: Jianhui
authors.initials: J
authors.lastname: Zhu
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Epstein
mesh_terms: D000328:Adult; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics; D002339:Carotid Arteries / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000378:metabolism / Q000503:physiopathology*; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008323:Mammary Arteries / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D052243:Resistin / Q000097:blood* / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E; D052243:Resistin