Influenza vaccination promotes stable atherosclerotic plaques in apoE knockout mice
Influenza vaccination promotes stable atherosclerotic plaques in apoE knockout mice
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DOI：
10.1016/j.atherosclerosis.2011.03.019
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发表时间：
2011-07-01
期刊：
影响因子：
5.3
通讯作者：
Oviedo-Orta, Ernesto
中科院分区：
文献类型：
--
作者：
Bermudez-Fajardo, Alexandra;Oviedo-Orta, Ernesto
目的：目前的证据表明季节性流感病毒感染与心血管疾病（CVD）之间的关系。接种甲型流感病毒的实验动物显示出与在人类中观察到的血栓形成并发症相似的血栓形成并发症。相反，一些流行病学研究和临床试验表明，流感疫苗接种可能对心血管疾病有保护作用。然而，这种保护作用背后的潜在机制尚未研究。我们的目的是研究流感疫苗接种对apoE（-/-）小鼠动脉粥样硬化斑块发展的影响。方法和结果：增加流感疫苗剂量的免疫效果（0.38、1.8、9和45 μ g/0.5mLVaxigrip（R），Sanofi-Aventis）对动脉粥样硬化形成的影响与用Pneumo 23（R）免疫的动物进行比较（肺炎球菌疫苗，Sanofi-Aventis）和用磷酸盐缓冲盐水（PBS）接种的对照组。与对照动物相比，用45 μ g/0.5mLVaxigrip（R）（用于免疫成人以抵抗流感的相同剂量）接种的动物产生较小的动脉粥样硬化病变，脂质含量较低，但平滑肌细胞和胶原蛋白较丰富。同时，他们表现出较低水平的干扰素γ（IFN γ），白细胞介素（IL）-2和肿瘤坏死因子α（TNF α），但较高水平的IL-4。此外，我们发现在用这些疫苗免疫的动物中，抗流感免疫球蛋白（IG）G1或抗Pneumo 23（R）IgM特异性抗体的水平以时间和剂量依赖的方式增加。结论：这些结果表明，接种流感疫苗可以通过促进更小和稳定的动脉粥样硬化斑块和诱导动脉粥样硬化保护性免疫应答来防止CVD的发展。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Objective: Current evidence suggests a relationship between seasonal Influenza viral infection and cardiovascular disease (CVD). Experimental animals inoculated with Influenza A virus have shown to develop thrombotic complications similar to those seen in humans. Conversely, several epidemiological studies and clinical trials have suggested that Influenza vaccination may have a protective effect on CVD. However, the potential mechanisms behind this protective effect remain unstudied. We aimed to study the effect of Influenza vaccination on atherosclerotic plaque development in apoE(-/-) mice.Methods and results: The effect of immunization with increasing doses of Influenza vaccine (0.38, 1.8, 9 and 45 mu g/0.5 mL Vaxigrip (R), Sanofi-Aventis) on atherogenesis was compared with that of animals immunized with Pneumo23 (R) (pneumococcus vaccine, Sanofi-Aventis) and control group inoculated with phosphate buffered saline (PBS). Animals vaccinated with 45 mu g/0.5 mL Vaxigrip (R), (the same dose used to immunize humans adults against Influenza) developed smaller atherosclerotic lesions with lower lipid content but richer in smooth muscle cells and collagen when compared with control animals. Concomitantly, they showed lower levels of interferon gamma (IFN gamma), interleukin (IL)-2 and tumor necrosis factor alpha (TNF alpha) but higher levels of IL-4. Furthermore, we found increased levels of anti-Influenza immunoglobulin (Ig) G1 or anti-Pneumo23 (R) IgM specific antibodies in a time and dose dependent fashion in animals immunized with these vaccines.Conclusions: These results indicate that vaccination against Influenza may protect against the development of CVD by promoting smaller and stable atherosclerotic plaques and by inducing atheroprotective immune responses. (C) 2011 Elsevier Ireland Ltd. All rights reserved.