Diabetes-induced accelerated atherosclerosis in swine
Diabetes-induced accelerated atherosclerosis in swine
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DOI：
10.2337/diabetes.50.7.1654
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发表时间：
2001-07-01
期刊：
影响因子：
7.7
通讯作者：
Kimsey, T
中科院分区：
文献类型：
--
作者：
Gerrity, RG;Natarajan, R;Kimsey, T
糖尿病患者发生动脉粥样硬化疾病的风险高于具有其他类似风险因素的非糖尿病个体，研究糖尿病加速动脉粥样硬化的潜在机制受到缺乏合适的人形动物模型的限制。在这项研究中，通过注射p细胞细胞毒素链脲佐菌素（STZ），导致β-细胞减少>80%和血浆葡萄糖增加至糖尿病水平。动物在没有外源性胰岛素的情况下维持长达48周。在患有糖尿病和高血糖症的猪中，与对照组相比，对单独和联合的糖尿病和高血糖症的猪的血浆：葡萄糖和胆固醇水平以及病变范围和严重程度进行定量。糖尿病对血浆胆固醇水平没有影响，但糖尿病/高血糖症（D-HL）猪发展为高血糖症，并且早在12周时就显示出主动脉嗜苏丹性是非糖尿病/高血糖症（NHL）猪的两倍（47.25 +/- 4.5 vs，24.0 +/- 4.6%）。在20周时，D-HL动物的冠状动脉狭窄明显大于N-HL动物（86 +/- 10 vs. 46 +/- 8%），冠状动脉病变主要发生在血管的前2-3 cm，并显示人形形态，D-HL猪的主动脉病变的胆固醇含量是N-HL猪的两倍，与N-HL猪相比，在D-HL猪的大体正常主动脉区域中油酸酯掺入胆固醇酯显著更大，并且归因于单核细胞中类似的升高的掺入。该大型研究表明，具有人形特征的糖尿病模型，包括高脂血症和严重的、加速的动脉粥样硬化可以在猪中可重复地诱导和维持。该模型在阐明糖尿病患者动脉粥样硬化加速的机制方面具有重要价值。
Patients with diabetes are at higher risk for atherosclerotic disease than nondiabetic individuals with other comparable risk factors, Studies examining mechanisms underlying diabetes-accelerated atherosclerosis have been limited by the lack of suitable humanoid animal models, In this study, diabetes was superimposed on a well-characterized swine model of atherosclerosis by injection of the p-cell cytotoxin streptozotocin (STZ), resulting in a >80% reduction in beta -cells and an increase in plasma glucose to diabetic levels. Animals were maintained without exogenous insulin for up to 48 weeks. Plasma:glucose and cholesterol levels and lesion extent and severity were quantified in swine with diabetes and hyperlipemia alone and in combination compared with controls, Diabetes had no effect on plasma cholesterol levels, but diabetic/hyperlipemic (D-HL) swine developed hypertriglyceridemia and showed a doubling in aortic sudanophilia over nondiabetic/hyperlipemic (NHL) swine as early as 12 weeks (47.25 +/- 4.5 vs, 24.0 +/- 4.6%). At 20 weeks, coronary artery stenosis was significantly greater in D-HL than in N-HL animals (86 +/- 10 vs. 46 +/- 8%), Coronary lesions predominantly arose in the first 2-3 cm of the vessels and displayed humanoid morphology, Aortic lesions in D-HL swine had double the cholesterol content of those in N-HL swine, and incorporation of oleate into cholesteryl ester was Significantly greater in grossly normal aortic areas of D-HL swine compared with N-HL and was attributed to similar elevated incorporation in monocytes, This large study demonstrates that a model of diabetes with humanoid characteristics, including hypertriglyceridemia and severe, accelerated atherosclerosis can be reproducibly induced-and maintained in swine. This model should potentially be of great value in elucidating mechanisms underlying the accelerated atherosclerosis seen in human diabetic individuals.