The impact of cyclophilin A small interfering RNA on the formation of atherosclerotic plaque in apolipoprotein E-deficient mice
10.3760/cma.j.issn.0253-3758.2014.07.014
- VernacularTitle:亲环素A小干扰RNA对载脂蛋白E基因敲除小鼠动脉粥样硬化斑块形成的影响
- Author:
Jinchuan YAN
1
;
Ying LI
;
Cuiping WANG
;
Wei YUAN
;
Zhongqun WANG
Author Information
1. 江苏大学附属医院心内科
- Keywords:
Atherosclerosis;
Cyclophilin A;
RNA small interfering
- From:
Chinese Journal of Cardiology
2014;(7):593-597
- CountryChina
- Language:Chinese
-
Abstract:
Objective The 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 .Methods Atherosclerostic 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 .Results CyPA-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.Conclusion Lentivirus-mediated CyPA silencing by siRNA could inhibit plaques progression and reduce local inflammation through the anti-inflammatory effects in this model .
