Although it is known that atherosclerosis is a systemic disease, the systemic effects of vascular injury have not been elucidated. Vascular permeability and inflammation are major players in the pathophysiology of atherosclerosis. Vascular permeability regulates recruitment and infiltration of immune cells to the site of injury, and therefore, controls disease progression. While the contribution of monocytes in plaque progression and destabilization has been extensively studied, the role of neutrophils, the most abundant white blood cell type, remains poorly understood. Few studies suggest that neutrophils may increase vascular permeability and promote plaque destabilization.1,2 Here, we used an albumin-binding contrast agent to assess whether (1) aortic wall injury triggers plaque progression in the brachiocephalic artery located distally to the site of injury and (2) whether neutrophils could be the link involved in this systemic response.Three groups of male ApoE-/- mice were imaged at 4, 8 and 12 weeks after commencement of the experimental protocol. (1) Mice were fed a high fat diet (HFD) to induce atherosclerosis (n=6); (2) Injured mice underwent endothelial denudation surgery3 followed by HFD (n=9); (3) Treated mice underwent vascular injury followed by HFD and pravastatin treatment (40mg/kg/day) (n=6). Control mice were imaged before HFD ± injury (n=6). In-vivo MRI: A 3T Philips Achieva system and a 23mm single-loop microscopy surface coil were used. Images were acquired 30min after gadofosveset administration (0.03mmol/kg). Acquisition parameters are summarized in Table 1. Flow cytometry: Neutrophil characterization was performed by using CD11b and Ly6G markers.DE-MRI using gadofosveset (Fig. 1) showed a significant enhancement of the brachiocephalic artery in mice that underwent vascular injury in the abdominal aorta (Fig. 1E-G) compared to the HFD group (Fig. 1B-D) suggesting that vascular injury may trigger a systemic response that accelerates lesion progression distally. Importantly, injured mice treated with statins showed decreased uptake, demonstrating the beneficial systemic effects of statins on lesion progression (Fig. 1H). Control mice showed little uptake (Fig. 1A). Histology revealed larger and advanced lesions after 12 weeks in the injury group with a surprisingly thick fibrous cap (Fig. 1J) as compared to the HFD (Fig. 1K) and statin-treatment groups (Fig. 1I), suggesting a more stable phenotype in the injury group. Quantitative analysis of vessel wall enhancement (Fig. 2A) and relaxation rate R1 (Fig. 2B) showed increased vascular permeability in the injury group 12 weeks after denudation as compared to other groups. The luminal area of the BCA was significantly decreased in the injury group as compared to the other groups (Fig. 2C). Quantitative analysis by flow cytometry revealed monocytosis and increased T-cell content under hyperlipidemic conditions. However, no significant differences were found between the HFD and injury group (data not shown). Interestingly, a significant increase of neutrophils was detected in the BCA of the injury group compared to other groups (Fig. 3A). In addition a significant correlation was detected between R1 values and neutrophil content in the BCA (Fig. 3B). These results suggest that neutrophils may be the systemic link between focal vascular injury and distal progression of atherosclerosis.Increased albumin leakage into the BCA vessel wall was observed in the aortic injury group demonstrating that vascular injury aggravates disease progression at a vascular segment located distally from the site of injury. BCA plaques in the injury group were characterised by larger and more stenotic atherosclerotic lesions with surprisingly thick fibrous cap. We also demonstrate that the systemic effects of vascular injury may be mediated by the mobilization of neutrophils that may represent a link between focal vascular injury and distal disease progression.