Gottingen minipig model of diet-induced atherosclerosis: influence of mild streptozotocin-induced diabetes on lesion severity and markers of inflammation evaluated in obese, obese and diabetic, and lean control animals
Gottingen minipig model of diet-induced atherosclerosis: influence of mild streptozotocin-induced diabetes on lesion severity and markers of inflammation evaluated in obese, obese and diabetic, and lean control animals
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DOI：
10.1186/s12967-015-0670-2
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发表时间：
2015-09-22
影响因子：
7.4
通讯作者：
Olsen, Lisbeth Hoier
中科院分区：
文献类型：
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作者：
Ludvigsen, Trine Pagh;Kirk, Rikke Kaae;Olsen, Lisbeth Hoier
背景资料：从药理学的角度来看，容易获得的，充分表征的心血管疾病的动物模型，包括动脉粥样硬化的相关体内标志物，对于评价新的候选药物是重要的。此外，考虑到糖尿病对人类患者动脉粥样硬化的影响，在这种模型的表征中包括这种疾病方面是高度相关的。本研究的目的是评估轻度链脲佐菌素诱导的糖尿病对饮食诱导的动脉粥样硬化minipigemodel.Methods的前和体内终点的影响：去势雄性哥廷根小型猪饲喂标准饲料（CD），致动脉粥样硬化饮食（HFD）或叠加轻度链脲佐菌素诱导的糖尿病（HFD-D）。在22或43周的饮食后，对炎症循环标志物（C-反应蛋白（CRP）、氧化低密度脂蛋白（oxLDL）、纤溶酶原激活物抑制剂-1、脂质和葡萄糖代谢以及冠状动脉和主动脉粥样硬化进行评价。通过参数数据的方差分析和非参数数据的Kruskal-Wallis检验评价组间差异。对于定性评估，应用Fisher精确检验。结果：总体而言，在两个时间点，与CD相比，HFD和HFD-D显示出增加的CRP、oxLDL和脂质参数。与HFD和CD相比，HFD-D显示葡萄糖代谢受损。在HFD和HFD-D的冠状动脉和主动脉中均观察到晚期动脉粥样硬化病变，主动脉中有更晚期的斑块发现，但HFD和HFD-D之间的病变严重程度或分布无差异。统计学上，甘油三酯是积极的（p = 0.0039），和高密度脂蛋白负相关（p = 0.0461）与主动脉斑块area.Conclusions：在这个模型中，观察到先进的冠状动脉和主动脉粥样硬化，炎症标志物的水平增加，临床相关动脉粥样硬化。未观察到轻度链脲佐菌素诱导的糖尿病对斑块面积、病变严重程度或炎症标志物的影响。
Background: From a pharmacological perspective, readily-available, well-characterized animal models of cardiovascular disease, including relevant in vivo markers of atherosclerosis are important for evaluation of novel drug candidates. Furthermore, considering the impact of diabetes mellitus on atherosclerosis in human patients, inclusion of this disease aspect in the characterization of a such model, is highly relevant. The objective of this study was to evaluate the effect of mild streptozotocin-induced diabetes on ex-and in vivo end-points in a diet-induced atherosclerotic minipig model.Methods: Castrated male Gottingen minipigs were fed standard chow (CD), atherogenic diet alone (HFD) or with superimposed mild streptozotocin-induced diabetes (HFD-D). Circulating markers of inflammation (C-reactive protein (CRP), oxidized low-density lipoprotein (oxLDL), plasminogen activator inhibitor-1, lipid and glucose metabolism were evaluated together with coronary and aortic atherosclerosis after 22 or 43 diet-weeks. Group differences were evaluated by analysis of variance for parametric data and Kruskal-Wallis test for non-parametric data. For qualitative assessments, Fisher's exact test was applied. For all analyses, p < 0.05 was considered statistically significant.Results: Overall, HFD and HFD-D displayed increased CRP, oxLDL and lipid parameters compared to CD at both time points. HFD-D displayed impaired glucose metabolism as compared to HFD and CD. Advanced atherosclerotic lesions were observed in both coronary arteries and aorta of HFD and HFD-D, with more advanced plaque findings in the aorta but without differences in lesion severity or distribution between HFD and HFD-D. Statistically, triglyceride was positively (p = 0.0039), and high-density lipoprotein negatively (p = 0.0461) associated with aortic plaque area.Conclusions: In this model, advanced coronary and aortic atherosclerosis was observed, with increased levels of inflammatory markers, clinically relevant to atherosclerosis. No effect of mild streptozotocin-induced diabetes was observed on plaque area, lesion severity or inflammatory markers.