Mechanism of the effect of rAd-APN gene on atherosclerosis in ApoE-/- mice
Received:November 23, 2015  
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DOI:10.3969/j.issn.1005-4847.2016.02.012
KeyWord:Adiponectin;Atherosclerosis;ApoE-/- mice;Inflammation;NF-κB signaling pathways
                 
AuthorInstitution
王雪梅 新疆医学动物模型研究重点实验室, 新疆医科大学第一附属医院临床医学研究院, 乌鲁木齐
魏琴 新疆医学动物模型研究重点实验室, 新疆医科大学第一附属医院临床医学研究院, 乌鲁木齐
张春 新疆医学动物模型研究重点实验室, 新疆医科大学第一附属医院临床医学研究院, 乌鲁木齐
姜涛 新疆医学动物模型研究重点实验室, 新疆医科大学第一附属医院临床医学研究院, 乌鲁木齐
段明军 新疆医学动物模型研究重点实验室, 新疆医科大学第一附属医院临床医学研究院, 乌鲁木齐
杨毅宁 新疆医学动物模型研究重点实验室, 新疆医科大学第一附属医院临床医学研究院, 乌鲁木齐
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Abstract:
      Objective Atherosclerosis (AS) is a common pathological basis of cardiovascular diseases. Adiponectin (APN) has been shown to have an anti-AS effect, and the underlying mechanisms, however, are largely unknown. Nuclear transcription factor κB (NF-κB) has also been regarded as a proatherogenic factor, mainly because of its regulation of a variety of the proinflammatory genes linked to AS. It is hypothesized that the inhibitory effects of APN on AS is through the inhibition of NF-κB signaling pathway. The aim of this study was to test the hypothesis via investigation and validation of the inhibitory effect of APN on AS in ApoE-/-mice, and to delineate the roles of NF-κB signaling pathway in modulating the APN effect on AS in vivo.Methods APN overexpression in ApoE-/- mice were mediated by transfecting adenovirus bearing a vector encoding for APN and enhanced green fluorescent protein (Ad-APN-eGFP). The AS in ApoE-/- mice was induced by feeding a high-fat diet. To validate the inhibitory effect of the adenovirus mediated APN overexpression on AS in the ApoE-/-mice. 120 male ApoE-/- mice aged 12 weeks were randomly and evenly assigned into two groups (60 mice per group), and were fed with a high-fat diet to induce AS. At 0 day, 2, 4, and 6 weeks of high-fat diet feeding. The 2 groups of mice were injected intravenously in the tail with either 100 μL (3.0×108 p.f.u) of Ad-eGFP virus (control group) or the same amount of Ad-APN-eGFP virus (APN group). Blood samples and aortic tissues were taken at 0 day, 4, and 8 weeks of high-fat diet feeding. For the blood samples, FABA was used to analyze the concentrations of blood lipids and ELIZA was used to test the concentrations of serum APN. For the aortic tissues, oil red O staining was used to detect the surface lesion percentage. Masson staining was used to evaluate the collagen content and fibrous cap thickness of the plaque area. Immunofluorescence method was used to detect APN and NF-κB p65 expression. Western blot was used to detect the expressions of APN,nuclear NF-κB p65 and the downstream factors of NF-κB pathway. Results APN inhibited the formation of atherosclerotic plaque in ApoE-/-mice. The lesion formation in aortic sinus was significantly inhibited (P<0.01). Compared with the control group, the oil red O staining showed that the surface area ratio of atherosclerotic lesions was decreased significantly in the Ad-APN group (P<0.001):the percentage of surface lesions in the 4 weeks groups was 27.78±8.64 vs. 33.02±5.18 (%); the 8 weeks groups was 31.58±5.87 vs. 52.16±5.79 (%).As the serum APN was increased,the concentration of TC, TG and LDL-C were significantly decreased(P<0.001 for all), and the growth of body weight was slowed down(P<0.05). APN effectively inhibited the expression of NF-κB nuclear protein p65 and inflammatory factors. Conclusions Adiponectin reduces the inflammatory reactions in atherosclerosis through inhibiting the NF-κB pathway.
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