APA Hamster Model for Diabetic Atherosclerosis. 2. Analysis of Lipids and Lipoproteins.

Abstract

Syrian hamsters of the APA strain (APA hamsters) have recently been shown to have atheromatous lesions in the aortic arches under diabetic condition induced by a single injection of streptozotocin (SZ). In that model, fatty streaks, which are the initial lesions of atherogenesis, develop by 6 weeks after the injection (WAI). In this study, we evaluated plasma lipid concentrations and lipoprotein profiles in diabetic APA hamsters at 6 WAI to reveal the early stage of atherogenesis clinicopathologically. As a result, by biochemical analysis, hyperglycemic APA hamsters showed signs of hypercholesterolemia and hypertriglyceridemia. Low-density lipoprotein (LDL) cholesterol significantly increased, but high-density lipoprotein (HDL) cholesterol significantly decreased. Agarose gel electrophoresis showed an obvious increase in the fractions of chylomicron, LDL and abnormal lipoprotein. Plasma LDL in diabetic animals was in a state more susceptible to oxidization. In addition, a significant increase in glycated LDL was also found in the diabetic animals by enzyme linked immunosorbent assay (ELISA). Moreover, lipid peroxidation product (4-hydroxynonenal (4 HNE))-adducted proteins and advanced glycation end-products (AGE) were immunohistochemically detected in the foam cells of the fatty streaks. These results revealed that diabetic APA hamsters had hyperlipidemia characterized by increases in chylomicron, LDL and abnormal lipoprotein, and suggested that oxidized LDL and/or glycated LDL might be actively uptaken by macrophages and play an important role in the initial stage of atherogenesis.

CD68/macrosialin: not just a histochemical marker

“…In such a model of diabetic atherosclerosis, rabbits develop early lesions (fatty streaks) by 6 weeks after streptozotocin administration along with hyperlipidemia. 51 In diabetic hamsters, Yamanouchi et al 52 observed expression of SR-AI, CD68, and receptor for advanced glycation endproducts (RAGE) mRNA in foam cells accumulated in early atherosclerotic lesions. Indeed, these observations suggested a likely role of CD68 in foam cell formation.…”

Amadori-modified glycated serum proteins and accelerated atherosclerosis in diabetes: Pathogenic and therapeutic implications

“…Syrian hamsters made diabetic with streptozotocin, which develop atheromatous lesions in the aortic arch, exhibit an elevated concentration of glycated LDL that is more susceptible to oxidation, and glycoxidative products are immunochemically detectable in the foam cells of fatty streaks (86). Glycated ethanolamine lipids have been identified in atherosclerotic plaques collected from diabetic and nondiabetic subjects (82).…”

Amelioration of the β‐cell dysfunction in diabetic APA hamsters by antioxidants and AGE inhibitor treatments

“…APA hamsters show hyperlipidemia as well as hyperglycaemia, and develop diabetic complications similar to human diabetic diseases, such as atherosclerosis [17][18][19][20] and nephropathy [21,22]. In this diabetic animal model, probucol treatment ameliorates glucose intolerance and increases the insulin-positive area as a percentage of the whole pancreas area without a cholesterol-lowering effect [23].…”