Sima A, Popov D, Starodub O, Stancu C, Cristea C, Stern D, Simionescu M
Institute of Cellular Biology and Pathology Nicolae Simionescu, Bucharest, Romania.
Lab Invest. 1997 Jul;77(1):3-18.
Diabetes is known to be accompanied by atherosclerotic disease and general cardiovascular complications. Hamsters were previously shown to develop hyperlipemia-induced atherosclerosis, similar in many respects to the human atherosclerotic process. To study the effect of hyperglycemia on heart vessels and valves, male Golden Syrian hamsters were rendered either diabetic or hyperlipemic and diabetic; controls were age-matched normal hamsters. At time intervals ranging from 2 to 24 weeks, animals were killed; plasma glucose, cholesterol, and lipid peroxides were measured; and the aortic arch and valves, coronary arteries, and heart microvessels were examined for ultrastructural modifications and for the presence of low-density lipoproteins (LDL), immunoglobulin G (IgG), and advanced glycation endproducts (AGE) proteins. Elevation of plasma glucose, peroxides, and cholesterol were observed in both diabetic as well as hyperlipemic and diabetic animals, along with characteristic diabetic changes: microangiopathy of the myocardium (ie, capillary narrowing, hyperplasia of basal lamina, and proliferation of extracellular matrix) and macroangiopathy of the aortic arch, valves, and coronary arteries (ie, intimal proliferation, fatty-streak formation, and calcification). LDL, IgG, and AGE-proteins were immunolocalized in focal deposits, ie, in the shoulder and cap of the plaques; these antigens were distributed diffusely in the extracellular space or within macrophage-derived foam cells and smooth muscle cells. Our findings indicate that hyperglycemia alone induces atherosclerotic lesions in the coronary arteries, aortic arch, and aortic valves as well as alterations of the extracellular matrix of heart microvessels and cardiomyocytes, changes which together may lead to cardiomyopathy, a common and severe complication of diabetes. In addition, the present study suggests that when hyperglycemia is accompanied by hyperlipemia, detectable amounts of modified LDL (possibly oxidized or glycated) and AGE are present in the intima of atherosclerotic arteries; and also that modified lipoproteins can act as immunoactive components of the atheroscerotic process generated by hyperglycemia.
已知糖尿病伴有动脉粥样硬化疾病和一般心血管并发症。先前研究表明，仓鼠会发生高脂血症诱导的动脉粥样硬化，在许多方面与人类动脉粥样硬化过程相似。为了研究高血糖对心脏血管和瓣膜的影响，将雄性叙利亚金黄仓鼠分为糖尿病组、高脂血症合并糖尿病组；对照组为年龄匹配的正常仓鼠。在2至24周的时间间隔内处死动物；测量血浆葡萄糖、胆固醇和脂质过氧化物；检查主动脉弓和瓣膜、冠状动脉以及心脏微血管的超微结构改变以及低密度脂蛋白（LDL）、免疫球蛋白G（IgG）和晚期糖基化终产物（AGE）蛋白的存在情况。在糖尿病组以及高脂血症合并糖尿病组动物中均观察到血浆葡萄糖、过氧化物和胆固醇升高，同时伴有典型的糖尿病变化：心肌微血管病变（即毛细血管狭窄、基底膜增生和细胞外基质增殖）以及主动脉弓、瓣膜和冠状动脉的大血管病变（即内膜增殖、脂肪条纹形成和钙化）。LDL、IgG和AGE蛋白免疫定位在局灶性沉积物中，即在斑块的肩部和帽部；这些抗原弥漫分布于细胞外空间或巨噬细胞衍生的泡沫细胞和平滑肌细胞内。我们的研究结果表明，单纯高血糖会导致冠状动脉、主动脉弓和主动脉瓣膜出现动脉粥样硬化病变，以及心脏微血管和心肌细胞的细胞外基质改变，这些变化共同可能导致心肌病，这是糖尿病常见且严重的并发症。此外，本研究表明，当高血糖伴有高脂血症时，在动脉粥样硬化动脉内膜中存在可检测量的修饰LDL（可能是氧化或糖基化的）和AGE；并且修饰的脂蛋白可作为高血糖产生的动脉粥样硬化过程的免疫活性成分。
