Current Research Projects

Brief overview of research projects that are in progress in the Vascular Surgery Research Laboratory:

"Molecular Mechanisms of Aneurysmal Degeneration" [NIH R01 HL56701-05, R.W. Thompson]. This program utilizes a mouse model of aortic aneurysms to elucidate critical molecular pathways in aneurysmal degeneration, principally through the use of genetically altered mice. The principal focus is on chemotactic molecules related to elastin and their receptors, and on various elastin-degrading members of the matrix metalloproteinase (MMP) family. A second component of the program is focused on delineating the molecular mechanisms by which doxycycline influences inflammatory cell expression of MMPs, using promoter-reporter constructs in cultured mononuclear phagocytes.

"Molecular Pathophysiology of Abdominal Aortic Aneurysms: Regulated Expression of Collagenases in AAA" [NIH R01 HL64332-01, R.W. Thompson]. The purpose of this project is to understand the factors regulating vascular smooth muscle cell (SMC) expression of collageneases-1 and -3, two important members of the MMP family. Studies involve immunohistochemistry and in situ hybridization in human aneurysm tissues, and use of promoter-reporter constructs in cultured human vascular SMC.

"Molecular Pathophysiology of Abdominal Aortic Aneurysms: Aneurysm Research Core" (NIH R01 HL64333-01, R.W. Thompson). This program supports a unique aneurysm research core laboratory, which provides human aortic tissues and the use of small animal models of aortic aneurysm to participating investigators in the Washington University Aneurysm Research Center.

"Molecular Pathophysiology of Abdominal Aortic Aneurysms: Oxidative Mechanisms" [NIH R01 HL64334-01, J. Heinecke]. This program utilizes sophisticated molecular analysis of human and murine aortic tissues to elucidate how different pathways of oxidative damage influence the development of aortic aneurysms. Studies involve the use of novel molecular "footprints" of oxidative damage, with a particular focus on MMPs and TIMPs, and the application of genetically altered mice deficient in enzymes specific to different oxidative pathways.

"Plasma MMP Levels in Patients with Aortic Aneurysms: Effects of Disease Progression and Doxycycline Treatment" [AHA Heartland Affiliate Research Grant-in-Aid 9951317Z, R.W. Thompson and D.M. Hovsepian]. The purpose of this project is to determine if plasma levels of MMP-9 can be used as biomarker of disease activity in patients with aortic aneurysms, and to examine the effects of treatment with doxycycline on plasma MMP-9 levels.

"Medical Interventions in the Management of Small Abdominal Aortic Aneurysms-MIMOSA" [R.W. Thompson and B.T. Baxter]. This project is a multi-institutional prospective randomized clinical trial intended to determine how treatment with doxycycline influences the expansion rate of small asymptomatic abdominal aortic aneurysms.

"Applications of Web-Based Artificial Neural Networks for the Diagnosis, Prognosis and Management of Abdominal Aortic Aneurysms" [R.W. Thompson]. This project represents a comprehensive computational approach to evaluate patients for their risks of having an aortic aneurysm, as well as to predict long-term outcomes for patients with aneurysms of all types. The project includes development of a web-based interactive system to provide information on aortic aneurysm disease, as well as for the conduct of clinical trials.

"Immunomodulating Cytokines in Abdominal Aortic Aneurysms" [P.J. Geraghty]. This program involves the use of human aortic tissues and mouse model of aortic aneurysm to elucidate the role of immunomodulating cytokines in aneurysmal degeneration.

"Mechanisms Underlying the Development of Ascending Aortic Aneurysms" [T.M. Sundt, Ruth Okamoto, and R.W. Thompson]. The purpose of this project is to examine how ascending aortic aneurysms differ from those arising in the abdominal aorta, particularly with respect to biochemical, morphological and biomechanical features.

"Biomechanical Properties of the Aneurysmal Aorta" [R.W. Thompson and R.P. Mecham]. This project involves quantitative biomechanical analysis of the aorta from mice with elastase-induced aneurysms, and how these features are influenced by targeted deletion of specific genes involved in aneurysmal degeneration.

“Interaction of Integrin avb3 and Matrix Metalloproteinases in Intimal Hyperplasia” (AHA Grant-in-Aid, E.T. Choi). This project involves the use of the mouse model of intimal hyperplasia to examine the role of a promiscuous integrin avb3 and its interaction with matrix metalloproteinases in smooth muscle cell migration leading to the development of intimal hyperplasia.

“Collagen-binding Integrins in Intimal Hyperplasia” (NIH K08, E.T. Choi). This project involves the use of human arterial tissues and mouse model of intimal hyperplasia to identify the smooth muscle cell receptors that bind to collagen and mediate cellular migration and proliferation on collagen leading to atherosclerosis and intimal hyperplasia.