Deficiency in endothelial nitric oxide synthase impairs myocardial angiogenesis

Cardiology Research Laboratory, Lawson Health Research Institute, London Health Sciences Centre, Departments of Medicine, Physiology, and Pharmacology, University of Western Ontario, London, Ontario, Canada N6A 4G5 We recently demonstrated that mice deficient in endothelial nitric oxide (NO) synthase (eNOS) have congenital septal defects and postnatal heart failure. However, the mechanisms by which eNOS affects heart development are not clear. We hypothesized that deficiency in eNOS impairs myocardial angiogenesis. Myocardial capillary densities were measured morphometrically in neonatal mouse hearts. In vitro tube formation on Matrigel was investigated in cardiac endothelial cells. In vivo myocardial angiogenesis was performed by implanting Matrigel in the left ventricular myocardium. Myocardial capillary densities and VEGF mRNA expression were decreased in neonatal eNOS / compared with neonatal wild-type mice ( P