Increased accumulation of nonenzymatically glycated fibrinogen in the renal cortex in rats

We have determined that the nonenzymatic glycation of fibrinogen altered its biological functions in vitro. Thrombin clottability of rat fibrinogen incubated with glucose decreased with increasing incubation time, but was not affected by the glucose concentration. Fibrin prepared from glycated fibrinogen showed a significant resistance in susceptibility to plasmin degradation. We also examined the in vivo distribution of glycated fibrinogen in renal cortex. Iodine labeled rat glycated or unglycated fibrinogen was injected into streptozocin-induced diabetic and control rats. No appreciable difference in the plasma disappearance rate in control rats was observed (half-lives in hours for glycated, 25.6 +/- 0.37; unglycated, 26.1 +/- 0.74). The radioactivity of fibrinogen retained to the renal cortex was calculated 24-hours after injection. In both control and diabetic rats, the retention rate of glycated fibrinogen in renal cortex was significantly higher than that of the unglycated. These results suggest that glycated fibrinogen may occur in a more resistant form to plasmin digestion with fibrin deposition as confirmed in in vitro studies. Therefore, we suggest that glycated fibrinogen may partly contribute to the development of diabetic microangiopathic lesions such as glomerulosclerosis.