title: Unmasking Silent Endothelial Activation in the Cardiovascular System Using Molecular Magnetic Resonance Imaging.
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.
authors.affiliation: 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.
authors.forename: Julie
authors.initials: J
authors.lastname: Belliere
authors.affiliation: 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.
authors.forename: Sara
authors.initials: S
authors.lastname: Martinez de Lizarrondo
authors.affiliation: 4. Division of Cardiovascular Medicine Radcliffe, Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Robin P
authors.initials: RP
authors.lastname: Choudhury
authors.affiliation: 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.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Quenault
authors.affiliation: 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.
authors.forename: Audrey
authors.initials: A
authors.lastname: Le Béhot
authors.affiliation: 2. Université Paul Sabatier, Toulouse, France. ; 5. Department of Microsurgery, Institut National de la Santé et de la Recherche Médicale (INSERM UMS006), Toulouse, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Delage
authors.affiliation: 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. ; 6. Department of Nephrology and Organ Transplantation, Faculté Purpan, CHU Rangueil, Toulouse, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Chauveau
authors.affiliation: 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.
authors.forename: Joost P
authors.initials: JP
authors.lastname: Schanstra
authors.affiliation: 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.
authors.forename: Jean-Loup
authors.initials: JL
authors.lastname: Bascands
authors.affiliation: 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.
authors.forename: Denis
authors.initials: D
authors.lastname: Vivien
authors.affiliation: 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.
authors.forename: Maxime
authors.initials: M
authors.lastname: Gauberti
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000175:diagnosis*; D002319:Cardiovascular System / Q000473:pathology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*
keywords: ICAM-1.; Inflammation; MPIO; USPIO; VCAM-1