4.7 Article

Increased 18F-FDG Uptake Is Predictive of Rupture in a Novel Rat Abdominal Aortic Aneurysm Rupture Model

期刊

ANNALS OF SURGERY
卷 261, 期 2, 页码 395-404

出版社

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/SLA.0000000000000602

关键词

AAA rupture; FDG-PET; IL-6; macrophage; MMP

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资金

  1. University of Michigan Cardiovascular Center Grant
  2. [NIH F32HL103065-01]
  3. [NIH RO1HL081629-01]

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Objective: To determine whether F-18-fluorodeoxyglucose (F-18-FDG) micro-positron emission tomography (micro-PET) can predict abdominal aortic aneurysm (AAA) rupture. Background: An infrarenal AAA model is needed to study inflammatory mechanisms that drive rupture. F-18-FDG PET can detect vascular inflammation in animal models and patients. Methods: After exposing Sprague-Dawley rats to intra-aortic porcine pancreatic elastase (PPE) (12 U/mL), AAA rupture was induced by daily, subcutaneous, beta-aminopropionitrile (BAPN, 300 mg/kg, N = 24) administration. Negative control AAA animals (N = 15) underwent daily saline subcutaneous injection after PPE exposure. BAPN-exposed animals that did not rupture served as positive controls [nonruptured AAA (NRAAA) 14d, N = 9]. Rupture was witnessed using radiotelemetry. Maximum standard uptakes for (18)FFDG micro-PET studies were determined. Aortic wall PAI-1, uPA, and tPA concentrations were determined by western blot analyses. Interleukin (IL)-1 beta, IL-6, IL-10, and MIP-2 were determined by Bio-Plex bead array. Neutrophil and macrophage populations per high-power field were quantified. Matrix metalloproteinase (MMP) activities were determined by zymography. Results: When comparing ruptured AAA (RAAA) to NRAAA 14d animals, increased focal F-18-FDG uptakes were detected at subsequent sites of rupture (P = 0.03). PAI-1 expression was significantly less in RAAA tissue (P = 0.01), with comparable uPA and decreased tPA levels (P = 0.02). IL-1 beta (P = 0.04), IL-6 (P = 0.001), IL-10 (P = 0.04), and MIP-2 (P = 0.02) expression, neutrophil (P = 0.02) and macrophage presence (P = 0.002), and MMP9 (P < 0.0001) activity were increased in RAAA tissue. Conclusions: With this AAA rupture model, increased prerupture F-18-FDG uptake on micro-PET imaging was associated with increased inflammation in the ruptured AAA wall. F-18-FDG PET imaging may be used to monitor inflammatory changes before AAA rupture.

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