Regular article
Vascular biology, atherosclerosis, and endothelium biology
Reverse Apolipoprotein A-I Mimetic Peptide R-D4F Inhibits Neointimal Formation following Carotid Artery Ligation in Mice

https://doi.org/10.1016/j.ajpath.2013.01.040Get rights and content

The ApoA-I mimetic peptide D-4F has demonstrated potent atheroprotective actions in vivo and in vitro. We investigated the effect of R-D4F (ie, the D-4F peptide with reverse order of amino acids) on intimal hyperplasia after vascular injury in a mouse model of carotid artery ligation. Adult male C57BL/6J mice were pretreated intraperitoneally with vehicle, D-4F (1 mg/kg), or R-D4F (1 mg/kg or 5 mg/kg) daily for 3 days; the mice were then subjected to left carotid artery ligation. All treatments were continued for 28 days after surgery. Neither D-4F nor R-D4F treatment affected serum lipid levels. Morphometric analysis showed that the occluded vessels had significant neointimal formation, compared with the uninjured arteries in vehicle-treated mice. Like the D-4F treatment, R-D4F treatment significantly (P < 0.05) inhibited intimal hyperplasia (−42%), local neutrophil and macrophage infiltration, and mRNA expression of the proinflammatory mediator monocyte chemotactic protein 1 (−55%) and vascular cell adhesion protein 1 (−53%), compared with vehicle. Furthermore, the vasoprotective effect of high-dose R-D4F was significantly enhanced, compared with the low dose. In cultured mouse RAW 264.7 macrophages, pretreatment with R-D4F also effectively inhibited lipopolysaccharide-induced leukocyte integrin CD11b expression, a key molecule for leukocyte infiltration. Taken together, these results suggest that R-D4F has significant anti-inflammatory features and facilitates prevention of neointimal formation after vascular injury in mice.

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Supported in part by awards from the Basic Research Project (Natural Science Foundation) of Jiangsu Province (BK2008220 to Z.Z. and BK2010324 to K.G.), the National Natural Science Foundation of China (81070096 and 81270197 to K.G. and 81141043, and 81270198 to Z.Z.), and the Project of Prospering Health by Science and Education in Jiangsu Province (RC2011045 to K.G.) and Jiangsu “333 Project” (BRA2012095 to K.G.).

L.D. and X.Q. contributed equally to this work.

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