The impact of cyclophilin A small interfering RNA on the formation of atherosclerotic plaque in apolipoprotein E-deficient mice.
- Author:
Jinchuan YAN
1
;
Ying LI
2
;
Cuiping WANG
2
;
Wei YUAN
2
;
Zhongqun WANG
2
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Apolipoproteins E; Cyclophilin A; biosynthesis; genetics; Disease Progression; Gene Silencing; Genetic Vectors; Inflammation; Lentivirus; Matrix Metalloproteinase 9; Matrix Metalloproteinases; Mice; Plaque, Atherosclerotic; RNA Interference; RNA, Small Interfering; Reverse Transcriptase Polymerase Chain Reaction; Transfection
- From: Chinese Journal of Cardiology 2014;42(7):593-597
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVEThe aim of this study was to determine whether inhibition of cyclophilin A by lentivirus-mediated RNA interference (RNAi) could inhibit progression of atherosclerotic plaques and increase collagen production.
METHODSAtherosclerostic plaque model was induced by rapid perivascular carotid silicone collar placement in ApoE(-/-) mice. The recombinant CyPA-RNAi-Lentivirus (CyPA-RNAi-LV) or negative control-green fluorescent protein-Lentivirus (NC-GFP-LV) were constructed and transfected into right carotid plaques, respectively. Using the local injection method, ApoE(-/-) mice carotid artery plaque were intervened 10 min in the silicone collar placement with 10 µl (1.0 × 10⁸ TU/ml) lentivirus vector. The areas and CyPA expression of plaques were analyzed by morphological observation, real-time polymerase chain reaction (RT-PCR) and Western blot respectively.
RESULTSCyPA-RNAi-LV not only prevented plaques progression ((9 085 ± 671) µm² to (18 021 ± 1 901) µm²), but also decreased plaque lipid content ((28.9 ± 6.3)% to (17.8 ± 4.5)%), increased plaque collagen content ((24.2 ± 4.8)% to (35.1 ± 5.2)%) at 6 weeks after lentivirus transfection. The intima/media ratio (0.36 ± 0.11 vs. 0.65 ± 0.12, P < 0.05) and degree of lumen stenosis (intima/lumen ratios, 0.18 ± 0.02 vs. 0.33 ± 0.03, P < 0.05) were also significantly reduced by CyPA-RNAi-LV. Moreover, RT-PCR analysis revealed downregulated expressions of proinflammatory cytokines and matrix metalloproteinases (MMP-9 -17.5%) in the CyPA-RNAi-LV group.
CONCLUSIONLentivirus-mediated CyPA silencing by siRNA could inhibit plaques progression and reduce local inflammation through the anti-inflammatory effects in this model.