Theranostics 2015; 5(11):1187-1202. doi:10.7150/thno.11835

Research Paper

Unmasking Silent Endothelial Activation in the Cardiovascular System Using Molecular Magnetic Resonance Imaging

Julie Belliere1,2, Sara Martinez de Lizarrondo3, Robin P. Choudhury4, Aurélien Quenault3, Audrey Le Béhot3, Christine Delage2,5, Dominique Chauveau1,2,6, Joost P. Schanstra1,2, Jean-Loup Bascands1,2, Denis Vivien3, Maxime Gauberti3✉

1. Inserm, Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM U1048, Institute of Cardiovascular and Metabolic Diseases, Toulouse, France.
2. Université Paul Sabatier, Toulouse, France.
3. Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM UMR-S U919, Serine Proteases and Pathophysiology of the Neurovascular Unit, Caen, France.
4. Division of Cardiovascular Medicine Radcliffe, Department of Medicine, University of Oxford, Oxford, UK.
5. Department of Microsurgery, Institut National de la Santé et de la Recherche Médicale (INSERM UMS006), Toulouse, France.
6. Department of Nephrology and Organ Transplantation, Faculté Purpan, CHU Rangueil, Toulouse, France

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Citation:
Belliere J, Martinez de Lizarrondo S, Choudhury RP, Quenault A, Le Béhot A, Delage C, Chauveau D, Schanstra JP, Bascands JL, Vivien D, Gauberti M. Unmasking Silent Endothelial Activation in the Cardiovascular System Using Molecular Magnetic Resonance Imaging. Theranostics 2015; 5(11):1187-1202. doi:10.7150/thno.11835. Available from http://www.thno.org/v05p1187.htm

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Abstract

Endothelial activation is a hallmark of cardiovascular diseases, acting either as a cause or a consequence of organ injury. To date, we lack suitable methods to measure endothelial activation in vivo. In the present study, we developed a magnetic resonance imaging (MRI) method allowing non-invasive endothelial activation mapping in the vasculature of the main organs affected during cardiovascular diseases. In clinically relevant contexts in mice (including systemic inflammation, acute and chronic kidney diseases, diabetes mellitus and normal aging), we provided evidence that this method allows detecting endothelial activation before any clinical manifestation of organ failure in the brain, kidney and heart with an exceptional sensitivity. In particular, we demonstrated that diabetes mellitus induces chronic endothelial cells activation in the kidney and heart. Moreover, aged mice presented activated endothelial cells in the kidneys and the cerebrovasculature. Interestingly, depending on the underlying condition, the temporospatial patterns of endothelial activation in the vascular beds of the cardiovascular system were different. These results demonstrate the feasibility of detecting silent endothelial activation occurring in conditions associated with high cardiovascular risk using molecular MRI.

Keywords: Inflammation, MPIO, USPIO, VCAM-1, ICAM-1.