13/01/2025 - Régis BLAISE : Phenotypic Alterations of Vascular Smooth Muscle Cells in Atherosclerosis and Alzheimer Disease

LES LUNDIS DE SAINT-ANTOINE

Bâtiment Kourilsky - 11h–12h

Salle des Conférences (Rez de Chaussée),

184 rue du Faubourg Saint-Antoine, Paris

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LUNDI 13 JANVIER 2025

Phenotypic Alterations of Vascular Smooth Muscle Cells in Atherosclerosis and Alzheimer Disease

Régis BLAISE

Associate Professor at Sorbonne University

 Membre de l'équipe de Guillaume DOROTHEE (regis.blaise@sorbonne-universite.fr)

Phenotypic alterations in vascular smooth muscle cells (VSMCs) play a crucial role in pathological vascular remodeling processes such as atherosclerosis and post-angioplasty restenosis. Additionally, these alterations are also implicated in vascular dysfunction in Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA).

During the last decade, we characterized a novel splicing variant of Adenylyl Cyclase 8 named AC8E, in transdifferentiated VSMCs in atherosclerosis. AC8E promotes VSMC transdifferentiation by reducing cAMP production. AC8E acts as a dominant negative by forming heterodimers with other full-length ACs, impeding the traffic of functional units towards the plasma membrane and inhibiting cyclase activity through its N-terminus domain.

In the context of AD and CAA, vascular deposits of amyloid peptides, primarily Aβ1-40, lead to a disruption of cerebral vascular integrity, resulting in changes in vascular tone implicated in cognitive impairment. Vascular tone is regulated by VSMCs and depends on the balance between cAMP and calcium pathways. Using real-time imaging in primary aortic and cerebrovascular VSMC cultures, we investigated the effects of Aβ1-40 on these signaling pathways. Our findings reveal that cerebral VSMCs, but not aortic VSMCs, exposed to Aβ1-40 acquire a hypercontractile phenotype, highlighting the distinct properties of VSMCs depending on their arterial bed of origin and further emphasize the vascular component in the pathology of AD and CAA.