Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 182, Issue 5, Pages 1932-1939Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2013.01.040
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Funding
- Basic Research Project (Natural Science Foundation) of Jiangsu Province [BK2008220, BK2010324]
- National Natural Science Foundation of China [81070096, 81270197, 81141043, 81270198]
- Project of Prospering Health by Science and Education in Jiangsu Province [RC2011045]
- Jiangsu 333 Project [BRA2012095]
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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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