Gene array analysis of a rat model of pulmonary arteriovenous malformations after superior cavopulmonary anastomosis

Abstract

Pulmonary arteriovenous malformations commonly develop in children who have undergone a cavopulmonary anastomosis as part of the palliative sequence for single-ventricle physiology. We developed a rat model of cavopulmonary anastomosis that results in pulmonary arteriovenous malformations that are angiographically and histologically similar to the human condition. We used this model to analyze the gene expression profile associated with pulmonary arteriovenous malformations developing after cavopulmonary anastomosis. Six Sprague-Dawley rats underwent right superior cavopulmonary anastomosis, allowing the left lung to serve as a control. Total RNA was isolated from each lung at death 8 months postoperatively and compared by using the Affymetrix Rat Microarray RAE230 2.0 GeneChip (Affymetrix, Santa Clara, Calif). One hundred thirty-seven genes demonstrated altered expression in the lungs after cavopulmonary anastomosis compared with that seen in the control lungs: 55 (40%) genes demonstrated increased expression, and 82 (60%) genes demonstrated decreased expression. Modulation of genes associated with angiogenesis and vascular remodeling was found, including angiopoietin-2, placental growth factor, several matrix metalloproteases, and several collagen subtypes. Genes with vasoactive properties, including endothelin 1 and endothelin receptor type B, demonstrated altered gene expression. Several members of the transforming growth factor beta superfamily signaling pathway also demonstrated altered expression. These changes in gene expression might have causative implications for pulmonary arteriovenous malformations that develop after cavopulmonary anastomosis.