Abstract 2677: Reduction In Tie-2+/flk-1+ Vascular Stem Cells In Thoracic Aortic Aneurysm With Dissections: A Novel Contributor To Acellular Lesion Development
Background. Ascending thoracic aortic aneurysms leading to type A dissections (TAAD) are a life-threatening disease triggered by a complex interactions between environmental and genetic factors. Pathologically, this disease is characterized by a progressive loss of vascular smooth muscle cells (SMCs) and extracellular elastic fibers in the aortic media. Apoptosis, a form of programmed cell death, has been shown to contribute to the loss of medial SMCs. However, little is known about the role of vascular progenitor or stem cells in the pathogenesis of aortic aneurysms.
Methods and Results. In this study we examined expression of Tie-2 (receptor for angiopoietin) and Flk-1 (receptor for vascular endothelial cell growth factor), two receptors critical for regulation of vascular stem cell survival and growth in the aortic lesions of patients with TAAD. Immunohistochemistry with specific antibodies against Tie-2 and Flk-1 showed a marked reduction in the numbers of Tie+/Flk+ cells in TAAD when compared to control aortas. There was also a change in the distribution pattern of vascular progenitor cells positive for both Tie-2 and Flk-1 in TAAD patients’ aortic tissues. Compared to normal control aortas, the Tie-2 and Flk-1 immunostained cells were much lower in intensity and scattered. In the regions with paucity of Tie-2+/Flk-1+ cells, there was an increased number of apoptotic cells as determined by in situ DNA end-labeling (TUNEL). Many of the Tie-2 and Flk-1 positive cells in TAAD showed poor morphology with nuclear degeneration and cytoplasmic fragmentation and disarray.
Conclusion. These results indicate a paucity of Tie-2+/Flk-1+ vascular stem cells in the aortic wall of patients with TAAD, implying that the stem cell capacity to regenerate SMCs is exhausted. Similar loss of stem cells is observed with Duchenne muscular dystrophy, where the regenerated capacity is significantly compromised. Stem cells loss may similarly impair the capacity of SMCs in aortic tissue in repair and regeneration, and ultimately lead to TAAD formation.