Ligation of the right lateral vitelline vein in chicken embryos (venous clip) results in changes in the intracardial blood flow patterns, and in functional and morphological cardiovascular defects.... Show moreLigation of the right lateral vitelline vein in chicken embryos (venous clip) results in changes in the intracardial blood flow patterns, and in functional and morphological cardiovascular defects. This demonstrates that blood flow, of which shear stress is a derivative, plays an important role in cardiovascular development. A general mechanism of shear stress sensing by endothelial cells remained to be elucidated. We postulate that the cytoskeleton functions as a central shear stress transducer, which uses a primary cilium for detection of low shear forces. During normal cardiogenesis we demonstrated that shear stress responsive genes lung Kruppel-like factor (KLF2) and endothelial nitric oxide synthase (NOS-3) are expressed in the endothelium and endocardium of structural lumen constrictions, where endothelin-1 (ET-1), a growth factor and vasoconstrictor, is absent and shear stress is high. After vitelline ligation KLF2 and NOS-3 were locally increased in the heart whereas ET-1 was down-regulated. Infusion of ET-1 or antagonists of the endothelin-A (ETA) and/or endothelin-B (ETB) receptor in the chicken embryonic circulation resulted in similar but less severe defects in cardiac function and morphology, demonstrating that components of the ET-1 pathway play a role in the development of cardiovascular defects in the venous clip model. Show less
