Elevated expressions of osteopontin and tenascin C in ascending aortic aneurysms are associated with trileaflet aortic valves as compared with bicuspid aortic valves

Objective: Ascending aortic aneurysms (AscAAs) are a highly lethal condition whose pathobiology remains to be poorly understood. Although most AscAAs occur in the presence of a trileaflet aortic valve (TAV), a bicuspid aortic valve (BAV) is a common congenital anomaly associated with an increased risk for an AscAA and dissection independent of functional valve pathology but secondary to inherent structural abnormality of the aorta. The objective of this investigation was to compare the patterns of gene expression in aortas between TAV and BAV patients with the aim of identifying markers for AscAAs. Methods: We used microarray analysis to first compare messenger RNA expressions between aneurysmal aortas from TAV patients (n=11) and those from BAV patients (n=11), identified genes overexpressed in TAV aneurysms, and compared expressions of the selected genes among TAV aneurysms, BAV aneurysms, and normal aortas (n=3). Finally, expressions of the selected genes were assessed by immunostaining of aortas from the TAV, BAV, and normal specimens. Results: Two overexpressed genes in the TAV group, osteopontin (OPN) and tenascin C (TNC), were consistently more highly expressed in TAV aneurysms than in BAV aneurysms and normal aortas as determined by real-time reverse transcriptase quantitative polymerase chain reaction and immunohistochemistry. Differential staining revealed that OPN protein was concentrated in the medial smooth muscle and that TNC protein was concentrated around the vasa vasorum. Conclusions: We identified two novel potential markers, OPN and TNC, that are strongly associated with TAV aneurysms. The roles of OPN and TNC in influencing extracellular matrix remodeling in AscAAs warrant further investigation.