Vascular Endothelial Growth Factor-B–Deficient Mice Display an Atrial Conduction Defect

Background—Vascular endothelial growth factors (VEGFs) and their receptors are essential regulators of vasculogenesis and angiogenesis in both embryos and adults. One of the factors with a still unknown physiological function is VEGF-B, which is expressed in many tissues, including the heart. Methods and Results—Mice carrying a targeted deletion in the VEGF-B gene were developed. In VEGF-B2/2 animals, no gross abnormalities were observed in organs that normally show high expression of VEGF-B, such as the heart, muscle, and kidney. Analysis of heart function by ECG showed that adult VEGF-B2/2 mice have an atrial conduction abnormality characterized by a prolonged PQ interval. VEGF- or basic fibroblast growth factor–induced corneal angiogenesis was similar in normal and VEGF-B2/2 mice. Conclusions—VEGF-B seems to be required for normal heart function in adult animals but is not required for proper development of the cardiovascular system either during development or for angiogenesis in adults. (Circulation. 2001; 104:358-364.) Key Words: growth substances n angiogenesis n electrocardiography n atrium n conduction Vasculogenesis and angiogenesis are complex processesthat generate the primary vascular system, which is essential for embryonic development and organ formation. Angiogenesis is also important in adults during reproduction