Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada.
Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada; Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada.
Atherosclerosis. 2018 Aug;275:88-96. doi: 10.1016/j.atherosclerosis.2018.05.044. Epub 2018 May 23.
Diabetic patients with no history of cardiac infarction have a prevalence of coronary atherosclerosis and a risk of heart attack equivalent to euglycemic patients who have coronary atherosclerosis and have suffered a prior myocardial infarction. Although several murine models of diabetes have been established, none of these show indications of cardiac events. In an attempt to establish a diabetic mouse model with coronary atherosclerosis and myocardial injury, we have fed hyperglycemic ApoE:Ins2 mice a western diet to enhance the dyslipidemic phenotype.
Five-week-old ApoE:Ins2 mice and ApoE controls were fed a diet, 0.15% cholesterol and 21% anhydrous milk lipids, until 25 weeks of age. Changes in lifespan, clinical and metabolic parameters were evaluated as well as atherosclerosis and heart injury.
In comparison to male ApoE, male ApoE:Ins2 mice presented with chronic hyperglycemia (30.8 ± 1.2 mM vs. 9.3 ± 0.5 mM) accompanied by extremely high levels of total plasma cholesterol (49.3 ± 6.3 mM vs. 30.1 ± 1.5 mM) and triglycerides (11.6 ± 1.7 mM vs. 2.36 ± 0.18 mM). These mice have atherosclerosis at multiple vascular sites, including aortic sinus, ascending and descending aorta, brachiocephalic artery and coronary arteries. In addition, myocardial infarcts and a significant reduction of the lifespan (close to 20% of survival vs. other groups) were observed. Distinctively, both strains of female mice presented a parallel increase in plasma lipids, atherosclerosis, and no effects on mortality.
We have established a diabetic mouse model, the western-diet-fed male ApoE:Ins2 mouse, with profound cardiovascular disease involving extensive atherosclerosis, coronary artery disease and myocardial infarct resulting in shortened lifespan.
没有心肌梗死病史的糖尿病患者存在冠状动脉粥样硬化的患病率和发生心肌梗死的风险，与患有冠状动脉粥样硬化且曾发生心肌梗死的血糖正常患者相同。虽然已经建立了几种糖尿病的小鼠模型，但没有一种显示出心脏事件的迹象。为了建立一种具有冠状动脉粥样硬化和心肌损伤的糖尿病小鼠模型，我们给高血糖 ApoE:Ins2 小鼠喂食西方饮食以增强血脂异常表型。
将 5 周龄的 ApoE:Ins2 小鼠和 ApoE 对照小鼠喂食含有 0.15%胆固醇和 21%无水乳脂的饮食，直到 25 周龄。评估了寿命、临床和代谢参数的变化以及动脉粥样硬化和心脏损伤。
与雄性 ApoE 相比，雄性 ApoE:Ins2 小鼠表现出慢性高血糖（30.8±1.2 mM 与 9.3±0.5 mM），同时伴有极高的总血浆胆固醇（49.3±6.3 mM 与 30.1±1.5 mM）和甘油三酯（11.6±1.7 mM 与 2.36±0.18 mM）水平。这些小鼠在多个血管部位发生动脉粥样硬化，包括主动脉窦、升主动脉和降主动脉、头臂动脉和冠状动脉。此外，还观察到心肌梗死和寿命显著缩短（接近其他组的 20%的存活率）。值得注意的是，两种雌性小鼠的血浆脂质、动脉粥样硬化均平行增加，且对死亡率没有影响。
我们建立了一种糖尿病小鼠模型，即喂食西方饮食的雄性 ApoE:Ins2 小鼠，其具有广泛的动脉粥样硬化、冠状动脉疾病和心肌梗死等严重的心血管疾病，导致寿命缩短。
