Aortic Atheromatous Lesions Developed in APA Hamsters with Streptozotocin induced Diabetes: A New Animal Model for Diabetic Atherosclerosis. 1. Histopathological Studies.

Abstract

Abstract:To develop an adequate animal model for atherosclerosis in large vessels of patients with diabetes, i.e. diabetic macroangiopathy, we induced diabetes in APA hamsters with a single injection of streptozotocin (SZ) and examined the aorta histopathologically and immunohistochemically. As a result, hyperglycemia and hyperlipidemia were continuously observed for 26 weeks after the SZ injection (WAI) in APA hamsters. Fatty streaks characterized by a subendothelial accumulation of many foam cells were observed, limited to the aortic arches as early as 6 WAI. In addition to larger fatty streaks developing with the duration of diabetes, fibrous plaques and plaques containing calcium deposits or cholesterol clefts developed at 26 WAI. These lesions are generally similar to the atheromatous lesions developed in humans. Moreover, depositions of apolipoprotein E and advanced glycation end-products immunohistochemically detected in the lesions were very similar to those found in humans. The diabetic APA hamster is therefore considered to be a useful model for studying the formation of atheromatous lesions in diabetic patients. Key words: APA hamster, atheromatous lesion, diabetes, macroangiopathy small vessels (microangiopathy) [19,23,33,35]. On the other hand, appropriate animal models of diabetic complications in large vessels (macroangiopathy) are quite rare [18,34], even though macroangiopathy is a leading cause of death in diabetic patients [7,10,29,38].Syrian hamsters of the APA strain (APA hamsters) have been developed in Japan [40] and are known to

Histopathological Studies of Aortic Dissection in Streptozotocin-Induced Diabetic APA Hamsters

“…This result was consistent with the distribution of atherosclerotic lesions of diabetic APA hamsters, because it has been reported that atherosclerotic lesions are found mainly in the aortic arch and rarely in the descending aorta in diabetic APA hamsters [12].…”

“…They are known to show a continuous diabetic state accompanied by its complications, such as glomerulosclerosis and atherosclerosis, following a single injection of streptozotocin (SZ) [4,7,12]. Recently, we observed Stanford type B aortic dissection in three diabetic APA hamsters when we investigated the effect of probucol on atherosclerosis in long-term diabetic APA hamsters.…”

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

“…We have recently demonstrated that the fatty streaks, which are the initial atheromatous lesions, developed in diabetic APA hamsters until 6 WAI [62]. 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.…”

“…Syrian hamsters of the APA strain (APA hamsters) have recently been shown to have atheromatous lesions in the aortic arches under diabetic conditions induced by a single injection of streptozotocin (SZ) [62]. In that model, fatty streaks, which are the initial lesions in atherogenesis, develop until 6 weeks after the injection (WAI).…”

Aortic ER Stress in Streptozotocin-Induced Diabetes Mellitus in APA Hamsters

“…In addition, Syrian hamsters of the APA strain (APA hamsters) are known to show a marked and continuous diabetic state accompanied by hypercholesterolemia and hypertriglycemia after a single injection of streptozotocin (SZ), which specifically attacks b-cells in pancreatic islets, and then develop atherosclerosis and glomerulosclerosis [10]. We previously reported that an analysis of the lipoproteins in cholesterol revealed a significant decrease in high density lipoproteins (HDL) and a significant increase in glycated low density lipoproteins (LDL) and oxidized LDLs [30]. Atheromatous lesions, so called "fatty streaks", which are characterized by a subendothelial accumulation of many foamy cells, are locally generated in the aortic arch of diabetic APA hamsters even at 6 weeks after SZ injection.…”