on November 2, 2006
Published online before print November 2, 2006, doi: 10.1161/01.ATV.0000251535.30191.60
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on April 11, 2006
Accepted on October 18, 2006
The CX3C Chemokine Fractalkine Induces Vascular Dysfunction by Generation of Superoxide Anions
Andreas Schäfer *;
From Medizinische Klinik und Poliklinik I (A.S., D.F., M.L., G.E., J.B.), Universitätsklinikum, Julius-Maximilians-Universität Würzburg, Germany; Deutsches Herzzentrum und 1. Medizinische Klinik (C.S., S.M.), Technische Universität München, Germany; Klinik und Poliklinik für Anästhesiologie (P.T.), Universitätsklinikum, Julius-Maximilians-Universität Würzburg, Germany; Institut für Klinische Biochemie und Pathobiochemie (M.E.), Julius-Maximilians-Universität Würzburg, Germany; Institut für Pathologie (S.S.), Klinikum rechts der Isar, Technische Universität München, Germany; Abteilung Gefässchirurgie (P.H.), Klinikum rechts der Isar, Technische Universität München, Germany.
* To whom correspondence should be addressed. E-mail: a.schaefer{at}medizin.uni-wuerzburg.de.
Objective--The chemokine fractalkine activates platelets and induces leukocyte adhesion to the endothelium. Expression of fractalkine and its receptor, CX3CR1, is elevated in coronary artery disease. We assessed the effects of fractalkine on vascular function in isolated rat aorta.
Methods and Results--CX3CR1 expression was demonstrated in rat aortic endothelial and smooth muscle cells by immunohistochemistry, Western blot, and polymerase chain reaction (PCR). Fractalkine (up to 1 µg/mL) did not directly induce contractile or relaxant responses when applied to rat aortic rings in organ baths. Short-term incubation with fractalkine (1 µg/mL) for 5 minutes did not affect vascular reactivity. Pretreatment of isolated rat aortic rings with fractalkine for 2 hours impaired acetylcholine-induced nitric oxide (NO)-mediated relaxation after preconstriction with phenylephrine in a concentration-dependent manner. The concentration response to the NO donor DEA-NONOate was significantly shifted to the right. The radical scavenger tiron normalized the attenuated acetylcholine-induced relaxation after fractalkine incubation. Aortic superoxide formation was enhanced by fractalkine, which was inhibited by diphenyleneiodonium but not by inhibitors of xanthine oxidase or NO synthase.
Conclusion--In addition to its role as a chemokine and adhesion molecule, fractalkine induces vascular dysfunction by stimulating vascular reactive oxygen species resulting in reduced NO bioavailability.
Key words: chemokines • endothelial dysfunction • nitric oxide • reactive oxygen species
This article has been cited by other articles:
 |
|
 |
|
  J. C. Sullivan, J. L. Pardieck, D. Doran, Y. Zhang, J.-X. She, and J. S. Pollock Greater fractalkine expression in mesenteric arteries of female spontaneously hypertensive rats compared with males Am J Physiol Heart Circ Physiol, April 1, 2009; 296(4): H1080 - H1088. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zernecke, E. Shagdarsuren, and C. Weber Chemokines in Atherosclerosis: An Update Arterioscler Thromb Vasc Biol, November 1, 2008; 28(11): 1897 - 1908. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. P. Yang, S. Mattagajasingh, S. Su, G. Chen, Z. Cai, K. Fox-Talbot, K. Irani, and L. C. Becker Fractalkine Upregulates Intercellular Adhesion Molecule-1 in Endothelial Cells Through CX3CR1 and the Jak Stat5 Pathway Circ. Res., November 9, 2007; 101(10): 1001 - 1008. [Abstract] [Full Text] [PDF]
|
|