Genetic manipulation of mice to study cardiovascular disease

Cardiovascular disease is the leading cause of death for both men and women in North America. Endothelial dysfunction plays a major part in the pathogenesis and progression of vascular disease. Therapeutic interventions that deliver vascular endothelial growth factor (VEGF) to hypoxic tissues have shown great promise in patients with cardiac or peripheral vascular disease by enabling the growth of new blood vessels. By contrast, production of VEGF by solid tumours induces neovascularization required for tumour growth. Given these results, it is no surprise that VEGF has received great attention in the fight against cancer. Currently, there are 33 active clinical trials using anti-VEGF approaches in attempts to cure this disease. The VEGF gene (Gen-Bank accession number NM_003376; gene ID: 7422) is complex and produces numerous isoforms that carry different biological properties. Understanding the mechanism(s) of production, storage, delivery and function of VEGF is fundamental if we are to use this factor effectively in treating patients.