APOE and Hyperglycemia: To investigate a direct role of TSP-1 in hyperglycemia-induced atherosclerosis, we generated TSP-1−/−/ApoE−/− double knockout mice that were subjected to STZ-induced hyperglycemia, as described in Methods; these mice were compared with age-matched STZ-induced hyperglycemic ApoE−/− littermates, both genotypes being at 18 weeks of age.