The invention relates to methods and compositions for treating and preventing cardiovascular disease, including but not limited to treating and preventing endothelial dysfunction in subjects having hyperhomocysteinemia, hyperglycemia, or a combination of hyperhomocysteinemia and hyperglycemia. As endothelial dysfunction is an indicator for atherosclerosis and cardiovascular disease, this treatment has general impact for early prevention and treatment for all cardiovascular disease. In particular, the present invention relates to methods and compositions for inhibiting calpain activity.
