Angiogenesis and remodeling in human thoracic aortic aneurysms.

Cardiovascular Research

PubMedID: 25139748

Kessler K, Borges LF, Ho-Tin-Noé B, Jondeau G, Michel JB, Vranckx R. Angiogenesis and remodeling in human thoracic aortic aneurysms. Cardiovasc Res. 2014;104(1):147-59.
AIMS
Human thoracic aneurysm of the ascending aorta (TAA) is a chronic disease characterized by dilatation of the aortic wall, which can progress to vessel dissection and rupture. TAA has several etiologies but all forms present common features, including tissue remodeling. Here, we determined and characterized the angiogenic process associated with TAA and its relation with wall remodeling.

METHODS AND RESULTS
Immunostaining for blood vessels showed an increased density of microvessels originating from the adventitia in the external medial layer of TAA compared to healthy aortas. Proteomic array analysis of 55 angiogenic factors in medial and adventitial layers showed different expression profiles in both tissue compartments between aneurysmal and healthy aortas. Quantification by ELISA confirmed that all forms of TAA contained higher levels of several pro- and anti-angiogenic factors, including angiopoietin-1 and -2, fibroblast growth factor-a, and thrombospondin-1 than healthy aortas. However, all groups showed comparable levels of VEGF-A. Quantitative RT-PCR demonstrated that angiopoietins were overexpressed in TAA media. Immunostaining and electron microscopy revealed that neovessels had defective endothelial junctions and poor mural cell coverage. This incomplete structure was associated with the accumulation of plasminogen and albumin in the media of TAA.

CONCLUSION
We describe, for the first time, leaky neovessel formation in TAA media in association with an imbalance of angiogenic factor levels. Although the initiating mechanisms of neo-angiogenesis in TAA and the potential etiology-related differences remain to be determined, our results suggest that neo-angiogenesis could participate in TAA wall remodeling and weakening through deposition of blood-borne zymogens.