Abstract-Transforming growth factor (TGF) receptor III (TGFR3), or -glycan, binds all 3 TGF ligands and inhibin with high affinity but lacks the serine/threonine kinase domain found in the type I and type II receptors (TGFR1, TGFR2). TGFR3 facilitates signaling via TGFR1/TGFR2 but also has been suggested to play a unique and nonredundant role in TGF signaling. Targeted deletion of Tgfbr3 revealed a requirement for Tgfbr3 during development of the coronary vessels. Coronary vasculogenesis is significantly impaired in null mice, with few vessels evident and numerous, persistent blood islands found throughout the epicardium. Tgfbr3-null mice die at embryonic day 14.5, the time when functional coronary vasculature is required for embryo viability. However, in null mice nascent coronary vessels attach to the aorta, form 2 coronary ostia, and initiate smooth muscle recruitment by embryonic day 14. Analysis of earlier developmental stages revealed defects in the epicardium. At embryonic day 13.5, these defects include an irregular and hypercellular epicardium with abundant subepicardial mesenchyme and a thin compact zone myocardium. Tgfbr3-null mice also displayed other defects in coronary development, including dysmorphic and distended vessels along the atrioventricular groove and subepicardial hemorrhage. In null mice, vessels throughout the yolk sac and embryo form and recruit smooth muscle in a pattern indistinguishable from heterozygous or wild-type littermates. These data demonstrate a requirement for Tgfbr3 during coronary vessel development that is essential for embryonic viability. Key Words: coronary vessels Ⅲ transforming growth factor  receptor Ⅲ mice, null C oronary artery disease is responsible for 54% of all cardiovascular disease in the United States. 1 Coronary vessels have a unique derivation from mesothelial cells that form a transitory structure termed the proepicardium. Proepicardial cells are transferred to the heart, form the epicardium, and give rise to endothelial cells, smooth muscle cells, and cardiac fibroblasts (reviewed elsewhere 2,3 ). Endothelial cells derived from the epicardium form a vascular plexus by the process of vasculogenesis. This vascular network attaches to the aorta and recruits epicardially derived mesenchyme to become vascular smooth muscle. The identification of the molecular and cellular processes that regulate coronary vessel development may provide insight into coronary vessel disease and reveal novel therapeutic opportunities.The transforming growth factor (TGF) family of growth factors regulates cell growth and differentiation in the cardiovascular system during both development and disease. 4 -6 Three ligands, TGF1, TGF2, and TGF3, 7-9 bind 4 cell surface proteins. These include two transmembrane serine/ threonine kinase receptors, the type I TGF receptor (TGFR1) and the type II TGF receptor (TGFR2). 10 -12 Several type I receptors, termed activin receptor-like kinases (ALKs), have been described. TGFR2 has a constitutively active cytoplasmic...
