Retraction: Platelet-derived RANTES mediates hypercholesterolemia-induced superoxide production and endothelial dysfunction.

Background—Hypercholesterolemia (HC) is known to elicit oxidative stress and impair endothelium-dependent vasodilation (EDV) in arterioles and large arteries. Although RANTES, a chemokine that promotes the recruitment of leukocytes, has been implicated in atherosclerosis, its role in HC has not been previously evaluated. Methods and Results—Wire myography, a cytochrome C reduction assay, and RT-PCR were used to assess the HC-induced responses of aortic rings from wild-type (WT), RANTES-deficient (RANTES / ), bone marrow chimeras (WT3WT, RANTES / 3WT, and WT3RANTES / ), and WT mice receiving antiplatelet serum (APS) to induce thrombocytopenia. HC led to superoxide (O2 ) production, Nox-2 expression, and EDV dysfunction in WT mice with a corresponding increase in plasma RANTES concentration. The HC-induced responses were absent in RANTES / , RANTES / 3WT chimeras, and APS-treated WT mice. Exposure of WT aortic rings to RANTES elicited EDV impairment and O2 production, which were blocked by incubation with heparin or metRANTES. Aortic rings from CD44-deficient mice exhibited responses similar to WT after RANTES incubation, suggesting that CD44 does not act as an auxiliary receptor in RANTES-mediated responses with HC. Conclusions—These findings are consistent with a mechanism whereby HC promotes platelet release of RANTES, inducing a glycosaminoglycanand CCR-dependent enhancement of O2 production with impairment of EDV. (Arterioscler Thromb Vasc Biol. 2008;28:000-000)