Ultrastructural changes and immunohistochemical localization of advanced glycation end products in the heart of streptozotocin-treated Mongolian gerbils.

This study was designed to clarify the developing mechanism of cardiomyopathy and vasculopathy in streptozotocin-treated Mongolian gerbils. Twenty male Mongolian gerbils (MG; 10-12 weeks old) were used, and 150 mg/kg of streptozotocin (STZ) was injected into the left femoral vein. Six control male MG were injected intravenously with normal saline. The animals showed severe hyperglycemia (up to 330 +/- 96.4 mg/dl) by 1 week after streptozotocin administration. At 1 week after STZ treatment, cardiomyocytes revealed no significant change, but unclear striated structures were demonstrated in cardiomyocytes at 4 weeks. After 1 year, anisocytosis was observed, and in the perinuclear region granular components were stained positively with periodic acid-Schiff reagent. Ultrastructurally, at 4 weeks and 1 year after STZ treatment, cardiomyocytes were irregular in size, and oval amorphous and lysosomal electron-dense bodies were observed in perinuclear and cytoplasmic regions. In coronary arteries, endothelial and medial cells revealed increased vesicles and intercellular collagen fibrils. Capillaries showed slight swelling of endothelial cells associated with the lamellar thickening of basement membrane and collagen fibrils in the perivascular regions. Immunohistochemically, advanced glycation end products (AGE) were observed in the cytoplasm of vascular and heart cells, and ultrastructurally the reaction products were demonstrated in the endoplasmic reticulum and lysosomes of cardiomyocytes and vascular cells in the STZ-treated Mongolian gerbils. AGE may play an important role not only in angiopathy but also in cardiomyopathy of STZ-treated Mongolian gerbils after STZ treatment.