Abstract | BACKGROUND: A role of CD40 (cluster of differentiation 40) is suggested in development of atherosclerosis plaques, especially in advanced plaques. However, the role of lentiviruses carrying small interfering RNA ( siRNA) of CD40 in progression and destabilization of advanced atherosclerotic plaques remains unknown. The aim of this study was to determine whether inhibition of CD40 signaling by lentivirus-mediated RNA interference (RNAi) could inhibit progression of atherosclerotic plaques and increase collagen production. METHODS:
Apolipoprotein E-deficient ( ApoE-/-) mice aged 10 weeks were fed a high-fat diet and a constrictive collar was placed around right carotid arteries of these mice to induce plaques formation. The recombinant CD40-RNAi-Lentivirus (CD40-RNAi-LV) or negative control- green fluorescent protein-Lentivirus (NC-GFP-LV) were constructed and transfected into right carotid plaques respectively eight weeks after surgery. RESULTS: CD40-RNAi-LV not only prevented plaques progression but also decreased plaques content of lipid, increased plaques content of collagen 6 weeks after lentivirus transfection. This effect reflected a marked decrease in the intima/media ratios (0.31 ± 0.04 vs 0.68 ± 0.05, P<0.05) and a diminished degree of lumen stenosis (intima/lumen ratios, 0.17 ± 0.04 vs 0.33 ± 0.40, P<0.05). Moreover, real-time polymerase chain reaction (RT-PCR) analysis of CD40-RNAi-LV group downregulated expressions of proinflammatory cytokines, chemokines and matrix metalloproteinases. CONCLUSIONS: Lentivirus-mediated CD40 silencing by siRNA treatment would be a new strategy to inhibit plaques progression and to reduce local inflammation through the antiinflammatory effects.
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Authors | Biao Wang, Hui Qian, Haibing Yang, Liangjie Xu, Wenrong Xu, Jinchuan Yan |
Journal | International journal of cardiology
(Int J Cardiol)
Vol. 163
Issue 1
Pg. 34-9
(Feb 10 2013)
ISSN: 1874-1754 [Electronic] Netherlands |
PMID | 21640399
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2011 Elsevier Ireland Ltd. All rights reserved. |
Chemical References |
- Apolipoproteins E
- CD40 Antigens
- Inflammation Mediators
- RNA, Viral
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Topics |
- Animals
- Apolipoproteins E
(administration & dosage, deficiency, genetics)
- CD40 Antigens
(administration & dosage, deficiency, genetics)
- Disease Progression
- Gene Silencing
- Genetic Therapy
(methods)
- Genetic Vectors
(administration & dosage, therapeutic use)
- HEK293 Cells
- Humans
- Inflammation Mediators
(administration & dosage, therapeutic use)
- Lentivirus
(genetics)
- Male
- Mice
- Mice, Knockout
- Plaque, Atherosclerotic
(genetics, pathology, therapy)
- RNA Interference
- RNA, Viral
(therapeutic use)
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