Alterations in TGF-β1 expression in lambs with increased pulmonary blood flow and pulmonary hypertension Article

Mata-Greenwood, E, Meyrick, B, Steinhorn, RH et al. (2003). Alterations in TGF-β1 expression in lambs with increased pulmonary blood flow and pulmonary hypertension . 285(1 29-1), 10.1152/ajplung.00171.2002

cited authors

  • Mata-Greenwood, E; Meyrick, B; Steinhorn, RH; Fineman, JR; Black, SM

fiu authors

abstract

  • The mechanisms responsible for pulmonary vascular remodeling in congenital heart disease with increased pulmonary blood flow remain unclear. We developed a lamb model of congenital heart disease and increased pulmonary blood flow utilizing an in utero placed aortopulmonary vascular graft (shunted lambs). Morphometric analysis of barium-injected pulmonary arteries indicated that by 4 wk of age, shunts had twice the pulmonary arterial density of controls (P < 0.05), and their pulmonary vessels showed increased muscularization and medial thickness at both 4 and 8 wk of age (P < 0.05). To determine the potential role of TGF-β1 in this vascular remodeling, we investigated vascular changes in expression and localization of TGF-β1 and its receptors TβRI, ALK-1, and TβRII in lungs of shunted and control lambs at 1 day and 1, 4, and 8 wk of life. Western blots demonstrated that TGF-β1 and ALK-1 expression was elevated in shunts compared with control at 1 and 4 wk of age (P < 0.05). In contrast, the antiangiogenic signaling receptor TβRI was decreased at 4 wk of age (P < 0.05). Immunohistochemistry demonstrated shunts had increased TGF-β1 and TβRI expression in smooth muscle layer and increased TGF-β1 and ALK-1 in endothelium of small pulmonary arteries at 1 and 4 wk of age. Moreover, TβRI expression was significantly reduced in endothelium of pulmonary arteries in the shunt at 1 and 4 wk. Our data suggest that increased pulmonary blood flow dysregulates TGF-β1 signaling, producing imbalance between pro- and antiangiogenic signaling that may be important in vascular remodeling in shunted lambs.

publication date

  • July 1, 2003

Digital Object Identifier (DOI)

volume

  • 285

issue

  • 1 29-1