TGFβ (transforming growth factor-β) blockade induces a human-like disease in a nondissecting mouse model of abdominal aortic aneurysm

Objective-Current experimental models of abdominal aortic aneurysm (AAA) do not accurately reproduce the major features of human AAA. We hypothesized that blockade of TGF beta (transforming growth factor-beta) activity-a guardian of vascular integrity and immune homeostasis-would impair vascular healing in models of nondissecting AAA and would lead to sustained aneurysmal growth until rupture. Approach and Results-Here, we test this hypothesis in the elastase-induced AAA model in mice. We analyze AAA development and progression using ultrasound in vivo, synchrotron-based ultrahigh resolution imaging ex vivo, and a combination of biological, histological, and flow cytometry-based cellular and molecular approaches in vitro. Systemic blockade of TGF beta using a monoclonal antibody induces a transition from a self-contained aortic dilatation to a model of sustained aneurysmal growth, associated with the formation of an intraluminal thrombus. AAA growth is associated with wall disruption but no medial dissection and culminates in fatal transmural aortic wall rupture. TGF beta blockade enhances leukocyte infiltration both in the aortic wall and the intraluminal thrombus and aggravates extracellular matrix degradation. Early blockade of IL-1 beta or monocyte-dependent responses substantially limits AAA severity. However, blockade of IL-1 beta after disease initiation has no effect on AAA progression to rupture. Conclusions-Endogenous TGF beta activity is required for the healing of AAA. TGF beta blockade may be harnessed to generate new models of AAA with better relevance to the human disease. We expect that the new models will improve our understanding of the pathophysiology of AAA and will be useful in the identification of new therapeutic targets

Focal Spot, Fall/Winter 2001

https://digitalcommons.wustl.edu/focal_spot_archives/1089/thumbnail.jp

Focal Spot, Fall 1982

https://digitalcommons.wustl.edu/focal_spot_archives/1032/thumbnail.jp

Focal Spot, Spring/Summer 1983

https://digitalcommons.wustl.edu/focal_spot_archives/1034/thumbnail.jp

A Spectral-Scanning Nuclear Magnetic Resonance Imaging (MRI) Transceiver

An integrated spectral-scanning nuclear magnetic resonance imaging (MRI) transceiver is implemented in a 0.12 mum SiGe BiCMOS process. The MRI transmitter and receiver circuitry is designed specifically for small-scale surface MRI diagnostics applications where creating low (below 1 T) and inhomogeneous magnetic field is more practical. The operation frequency for magnetic resonance detection and analysis is tunable from 1 kHz to 37 MHz, corresponding to 0-0.9 T magnetization for ^1H (hydrogen). The concurrent measurement bandwidth is approximately one frequency octave. The chip can also be used for conventional narrowband nuclear magnetic resonance (NMR) spectroscopy from 1 kHz up to 250 MHz. This integrated transceiver consists of both the magnetic resonance transmitter which generates the required excitation pulses for the magnetic dipole excitation, and the receiver which recovers the responses of the dipoles

Focal Spot, Fall 1985

https://digitalcommons.wustl.edu/focal_spot_archives/1041/thumbnail.jp

Focal Spot, Fall/Winter 1980

https://digitalcommons.wustl.edu/focal_spot_archives/1027/thumbnail.jp

Focal Spot, Winter 2004/2005

https://digitalcommons.wustl.edu/focal_spot_archives/1098/thumbnail.jp

Focal Spot, Fall/Winter 2003/2004

https://digitalcommons.wustl.edu/focal_spot_archives/1095/thumbnail.jp