Thrombospondin-1: A proatherosclerotic protein augmented by hyperglycemia

Diabetes is increasing rapidly in the United States. One of the characteristics of this disease is accelerated atherosclerosis. Thrombospondin-1 (TSP-1) has been shown to be involved in atherosclerosis and up-regulated in the tissues of diabetic patients and in animal models of diabetes. Among other actions, TSP-1 has been shown to increase DNA synthesis in vascular smooth muscle cells; however, the specific genes increased have not been completely identified. Further, the influence of hyperglycemia on TSP-1-induced gene expression has not been fully determined. The present study demonstrates that TSP-1 causes the up-regulation of several genes involved in atherosclerosis and diabetes and that hyperglycemia has a substantial effect on this process. Understanding the apparent complex interaction between hyperglycemia and TSP-1 will help identify therapeutic targets and aid in the development of anti-TSP-1 strategies to reduce vascular disease in diabetes.