Abstract 353: Diabetes Induces Increased Expression of Matricellular Osteoblast Factor Periostin and Inhibits the Calcification Inhibitor Matrix Gla Protein (mgp) in Rat Aorta

Abstract

It is increasingly recognized that diabetes is associated with increased risk of cardiovascular events and vascular calcification. To understand the mechanism of vascular calcification in diabetes we used a rat model of type 2 diabetes. Rats were fed ad libitum with diet containing 45 kcal % fat (soybean oil and lard with 0.95 mg cholesterol /gram of lard), 35 kcal % carbohydrates and 20% kcal protein (HF diet) for eight weeks, followed by a single low dose of stz (30mg/kg intra peritoneally). Rats were then allowed to developed diabetes for sixteen weeks. Average blood glucose in diabetic HF rats 517.6mg/dl vs 87.8mg/dl in HF rats. The expression and immunohistochemical changes were analyzed in aorta of these rats after sixteen weeks of diabetes. Conformational specific gamma carboxylated (Gla) and undercarboxylated (Glu) MGP antibodies were used to assess the expression of Gla and Glu MGP in control and diabetic HF rat aorta. Western blot analysis show significantly reduced expression of Gla MGP in diabetic HF rat aorta and higher Glu MGP expression compared to control rat aorta suggesting that diabetic conditions inhibit the gamma carboxylation of MGP in aorta, gamma carboxylation modification is necessary for the MGP to work as physiological calcification inhibitor. Similarly, immunohistochemical analysis of diabetic HF rat and control rat aorta show increased staining of Glu MGP than Gla MGP compared to control rat aorta further confirm our Western data that modification of Gla MGP is inhibited in diabetic HF rats. Furthermore, immuno-histochemical data also show significantly increased in diabetic HF rat aorta expression of Periostin a matricellular osteoblast specific factor expression compared to control rat aorta. Our findings suggest that active diabetes impair the physiological properties of calcification inhibitor Gla MGP in aorta and increases the osteogenic factors in diabetic HF rats. Increased expression of osteoblastic factor and inhibition of Gla MGP suggests that diabetic HF rat aorta is under active transformation to become more bone like, precursor of arterial calcification.