PATHOBIOLOGIC STUDIES OF ANEURYSM WEAKENING

Description of projects available to graduate students:
We are investigating the central hypothesis that, once formed, the wall of an aneurysm progressively weakens as a result of increasingly discordant repair/remodeling mechanisms and/or increasing severity of proteolysis, and these are both mediated by the local biophysical environment. Specifically, we believe that regions of concentrated mechanical wall stress lead to localized AAA degeneration by causing an alteration in the balance between ECM synthesis and degradation. We also believe that a separate mechanism exists in those regions of the AAA wall adjacent to an appreciable layer of intraluminal thrombus (ILT), in that resulting attenuated oxygen diffusion to the AAA wall results in cellular hypoxia, followed by additional alterations in the balance between ECM synthesis and degradation. We are addressing these hypotheses by evaluating the gross morphology of AAA wall tissue freshly excised from regions of known wall stress or oxygen tension. In addition, the overall balance between ECM synthesis and degradation are being evaluated in this tissue by measuring ECM synthesis and degradation, such as matrix metalloproteinases (MMPs), plasminogen activators, tropoelastin and procollagens.

Techniques graduate student will learn:
RT-PCR; Western blotting; ELISA; immunohistochemistry; multi-photon imaging.