Published online before print August 17, 2007, doi: 10.1161/CIRCRESAHA.107.152082
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Submitted on March 27, 2007
Revised on July 2, 2007
Accepted on August 7, 2007
Coronary Vessel Development Is Dependent on the Type III Transforming Growth Factor 
Receptor
Leigh A. Compton ;
From the Departments of Pharmacology (L.A.C., D.A.P., J.V.B.) and Pediatrics (C.B.B.), Vanderbilt University Medical Center, Nashville, Tenn.
* To whom correspondence should be addressed. E-mail: joey.barnett{at}vanderbilt.edu.
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 • transforming growth factor
receptor •
mice, null
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