The potential role of resistin in atherogenesis.
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.
Burnett
Mary Susan
MS
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
Lee
Cheol W
CW
Kinnaird
Tim D
TD
Stabile
Eugenio
E
Durrani
Sarfraz
S
Dullum
Mercedes K
MK
Devaney
Joseph M
JM
Fishman
Craig
C
Stamou
Sotiris
S
Canos
Daniel
D
Zbinden
Stephan
S
Clavijo
Leonardo C
LC
Jang
Gil Jin
GJ
Andrews
James A
JA
Zhu
Jianhui
J
Epstein
Stephen E
SE
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*
D001057:Apolipoproteins E; D052243:Resistin