VCAM-1 Target in Non-Invasive Imaging for the Detection of Atherosclerotic Plaques

Figures

• 

  Figure 1. The different stages of the development of atherosclerosis, from endothelial dysfunction to plaque rupture with thrombosis.

• 

  Figure 2. The structure of VCAM-1 and its α4β1 integrin binding regions. Human VCAM-1 has two splice variants with seven or six domains. Murine VCAM-1 has also two splice variants with seven or three domains. The α4β1 integrin binds to D1 of all the splice variants, but it binds to D4 if this domain is present and depending on the activation state of the α4β1 integrin.

• 

  Figure 3. The signalling pathways initiated downstream of VCAM-1 binding with α4β1 integrin. The binding of the leucocyte to VCAM-1 and its complex ezrin-moesin (ERM) activates Rac-1. Rac-1 induces two pathways: (1) reactive oxygen species (ROSs), which activate matrix metalloproteinases (MMPs), protein kinase Cα (PKCα) and protein tyrosine phosphatase 1B (PTP1B) and which finally lead to the disruption of the endothelial cells’ (ECs) junctions and the (2) p21-activated protein kinase (PAK)-myosin light chain (MLC) pathway, which leads to actin remodelling.

• 

  Figure 4. Images from the study of Chan et al. [87]. Detection of vulnerable inflamed plaques in mouse carotid arteries by in vivo MRI after administration of dual-MPIO (on the left) or control IgG-MPIO (on the right). In post-injection imaging after 2 h, the hypointensity signal in the aortic root was detected for dual-MPIO, but no change was observed for the control MPIO. Field of view: 25.6 mm × 25.6 mm. Acquisition matrix: 256 × 256. Reproduced with permission from Chan et al., Imaging Vulnerable Plaques by Targeting Inflammation in Atherosclerosis Using Fluorescent-Labeled Dual-Ligand Microparticles of Iron Oxide and Magnetic Resonance Imaging; published by J. Vasc. Surg., 2018.

• 

  Figure 5. Images from the study of Bruckman et al. [99] Magnetic resonance imaging of the abdominal aorta of ApoE−/− mice injected with VCAM-TMV demonstrated a positive enhancement of the arterial wall after 90 min of injection (on the right) compared to the images pre-injection (on the left). Field of view = 29.8 mm × 29.8 mm. Acquisition matrix: 256 × 256.

• 

  Figure 6. Images from the study of Bridoux et al. [115]. Detection of atherosclerotic lesions in the mouse aortic arch (Ao), near the heart (H), by in vivo β-CUBE imaging system after administration of [18F]AlF(RESCA)-cAbVCAM1-5 (top), but not after administration of control unlabelled cAbVCAM1-5 Nb (bottom). The kidneys (K), bladder (Bl) and bone structures (Bs) are also visible on the images. Voxel size of 0.4 and 0.5 mm. Open access article (Bridoux et al., Improved Detection of Molecular Markers of Atherosclerotic Plaques Using Sub-Millimeter PET Imaging; published by Molecules, 2020) distributed under the Creative Commons Attribution License.