Advances in imaging angiogenesis and inflammation in atherosclerosis

Abstract

Advances in imaging technology have provided powerful tools for dissecting the angiogenic and inflammatory aspects of atherosclerosis. Improved technology along with multi-modal approaches has expanded the utilisation of imaging. Recent advances provide the ability to better define structure and development of angiogenic vessels, identify relationships between inflammatory mediators and the vessel wall, validate biological effects of anti-inflammatory and anti-angiogenic drugs, delivery and/or targeting specific molecules to inflammatory regions of atherosclerotic plaques.

Figure 1. Depiction of “inside-out” and “outside-in” theories of vascular inflammation

The “outside-in” theory assumes that inflammatory cell enter the vessel wall from the luminal side. The “outside-in” theory predicts that the inflammatory cells gain entry to the vessel wall via adventitial vasa vasorum. Printed with permission by Oxford University Press: Maiellaro K, Taylor WR. The role of the adventitia in vascular inflammation. Cardiovasc Res 2007; 75: 640–648. (23).

Figure 2. Correlation of multi-modal imaging of neoangiogenesis in atherosclerotic plaque

Three imaging techniques were used to correlate and validate data. a) DCE-MRI map of area under the curve following gadolinium injection; b) CD31 probed cross-sections of abdominal aorta; c) FDG PET image of ¹⁸F-FDG uptake in abdominal aorta of a hypercholesterolaemic rabbit. Printed with permission from Wollters Kluwer Health: Calcagno C, et al. Detection of neovessels in atherosclerotic plaques of rabbits using dynamic contrast enhanced MRI and 18F-FDG PET. Arterioscler Thromb Vasc Biol 2008; 28: 1311–1317. (44).

Figure 3. Imaging the effects of simvastatin on plaque inflammation

PET images pre- and post- ¹⁸FDG uptake in human subjects with potential risk of atherosclerosis, who received diet management or diet management + simvastatin treatment. Arrows indicate ¹⁸FDG uptake into plaque. Printed with permission from Elsevier Inc.: Tahara N, et al. Simvastatin attenuates plaque inflammation: evaluation by fluorodeoxyglucose positron emission tomography. J Am Coll Cardiol 2006; 48: 1825–1831 (45).

Figure 4. Intravital microscopy imaging (IVM) of leukocyte rolling mechanisms

P-selectin dependent leukocyte rolling in mesenteric veins of Prdx1^−/− mice was detected by IVM. Mice were infused with either (a) a P-selectin aptamer inhibitor vs. a scrambled aptamer or (b) an anti-P-selectin Ig vs. control Ig. Endogenous leukocytes are indicated by arrows. Printed with permission from Lippincott Williams & Wilkins: Kisucka J, et al. Peroxiredoxin1 prevents excessive endothelial activation and early atherosclerosis. Circ Res 2008; 103: 598–605 (79).