//V. Di Cataldo, J. Debatisse, A. Geloen, E. Labaronne, E. Loizon, A. Millon, C. Crola Da Silva, L. Mechtouff, E. Canet-Soulas … and coll. 2021 April. Brain Commun

V. Di Cataldo, J. Debatisse, A. Geloen, E. Labaronne, E. Loizon, A. Millon, C. Crola Da Silva, L. Mechtouff, E. Canet-Soulas … and coll. 2021 April. Brain Commun

«  Nous avons réalisé une étude préclinique mono-centrique prospective pour évaluer l’athérosclérose carotidienne et ses conséquences cérébrales chez le macaque cynomolgus en combinant l’imagerie et l’analyse génomique. Dans ce modèle d’athérosclérose induit par un régime et exploré en imagerie in-vivo et par analyse génomique, nous montrons (i) que les macaques cynomolgus présentent des caractéristiques de plaques vulnérables similaires à celles des patients ainsi que le même profil génomique, (ii) l’imagerie cérébrale met en évidence une neuro-inflammation au niveau du cortex frontal et des signes neuro-vasculaires. L’élévation de l’inflammation corticale et un défaut d’activité des plexus choroïdes étaient associés au profil d’athérosclérose à haut risque. » Emmanuelle Canet-Soulas

Abstract

Atherosclerosis is a chronic systemic inflammatory disease, inducing cardiovascular and cerebrovascular acute events. A role of neuroinflammation is suspected, but not yet investigated in the gyrencephalic brain and the related activity at blood−brain interfaces is unknown. A non-human primate model of advanced atherosclerosis was first established using longitudinal blood samples, multimodal imaging and gene analysis in aged animals. Non-human primate carotid lesions were compared with human carotid endarterectomy samples. During the whole-body imaging session, imaging of neuroinflammation and choroid plexus function was performed. Advanced plaques were present in multiple sites, premature deaths occurred and downstream lesions (myocardial fibrosis, lacunar stroke) were present in this model. Vascular lesions were similar to in humans: high plaque activity on PET and MRI imaging and systemic inflammation (high plasma C-reactive protein levels: 42 ± 14 µg/ml). We also found the same gene association (metabolic, inflammatory and anti-inflammatory markers) as in patients with similar histological features. Metabolic imaging localized abnormal brain glucose metabolism in the frontal cortex. It corresponded to cortical neuro-inflammation (PET imaging) that correlated with C-reactive protein level. Multimodal imaging also revealed pronounced choroid plexus function impairment in aging atherosclerotic non-human primates. In conclusion, multimodal whole-body inflammation exploration at the vascular level and blood−brain interfaces identified high-risk aging atherosclerosis. These results open the way for systemic and central inflammation targeting in atherosclerosis in the new era of immunotherapy.

juillet 2021|