Abstract 1456: Transcriptional Profiling of the Coronary Artery Intimal Lesions in Pulmonary Atresia with Intact Ventricular Septum: Expression of Specific Collagens, Proteoglycan Core Proteins and Glycosaminoglycans
Background-In some cases of pulmonary atresia and intact ventricular septum (PA/IVS), the coronary arteries have intimal occlusive lesions characterized by a population of spindle cells in an abundant extracellular matrix (ECM). The nature of the cells and the composition of the matrix are not well characterized.
Methods and Results-Following laser capture microdis-section of coronary artery intimal lesions, RNA was extracted, amplified and hybridized to the Affymetrix Human X3P GeneChip containing probe sets that define 47,000 human genes. Chip data was analyzed using the GeneSifter statistical software package. Transcripts for multiple ECM components were detected, including a variety of collagen α chains and specific proteoglycan (PG) core proteins including decorin, fibromodulin, glypican-6, lumican, syndecan-2 and versican. Elevated levels of transcripts for the enzymes involved in keratin sulfate biosynthesis, sulfation of PG, and biosynthesis of glucosaminoglycans (GAG) were also detected, as well as transcripts for some hyaluronan binding proteins. The gene expression findings were validated using immunohistochemical analysis of coronary artery lesions.
Conclusions-The coronary artery intimal lesions in PA/IVS contain transcripts for multiple collagens, specific PG core proteins and enzymes capable of synthesizing GAG. The ECM composition of these coronary artery intimal lesions has components that are similar to those that accumulate in rodent artery injury models and in adult restenosis lesions. Analysis of these rare pediatric coronary artery intimal lesions may provide new insights into the pathobiology of human arterial intimal disease.