Team M. LAFFARGUE

Cell Responses in Arterial Stress : Impact on cardiovascular diseases (CREATED)
Our team groups together experts in cell signalling dedicated to the understanding of molecular mechanisms involved in vascular homeostasis (PI3K/mTOR pathways) and modulated by various stresses in pathologic conditions or related to aging (mechanical, oxydative or metabolic stresses, inflammation). In collaboration with clinicians from the hospital Toulouse Rangueil, we develop original pre-clinical models of arterial lesions with the aim to improve actual treatments of atherosclerosis and the prevention of transplant vasculpathies causing organ rejection.
Team members

Muriel LAFFARGUE

Nathalie AUGE

Stéphanie GAYRAL

Damien RAMEL

Natalia Smirnova

Caroline CAMARE

Anne Darmon

Honora Labrana

Isra MENTOURI

Laura Mickiewicz

Nicole MALET

Anne NEGRE-SALVAYRE

Robert SALVAYRE

Didier CARRIE

Kevin CORMIER

Arnaud DEL BELLO
Control of endothelial homeostasis in response to mechanical stress : Impact on arterial diseases

Coordinators : Stéphanie GAYRAL, Caroline CAMARE, Anne NEGRE-SALVAYRE, Muriel LAFFARGUE
Environnemental hemodynamic milieu controls endothelial cell activation and their maintenance of their barrier function. Study of the perturbations of mechanosensors able to integrate these bio-mechanics stimuli and their associated signalling pathways associated with pathological conditions, will allow us to propose new therapeutic avenues to prevent endothelial dysfunction.
Cell signaling in vascular smooth muscle cells in normal and pathological conditions

Coordinators : Nathalie AUGE, Damien RAMEL, Natalia SMIRNOVA, Anne NEGRE-SALVAYRE, Muriel LAFFARGUE
Smooth muscle cells are at the center stage of the arterial responses in normal and pathological conditions. We investigate their signaling pathways to decipher the molecular mechanisms leading to their deregulation found in cardiovascular diseases such as atherosclerosis or explant rejection but also in disturbed metabolic conditions such as diabetes.
New therapeutic strategies for arterial diseases : Pre-clinical models and translational approaches towards patients

Coordinators : Didier CARRIE, Natalia SMIRNOVA, Anne NEGRE-SALVAYRE et Muriel LAFFARGUE
With the aim to test new therapeutic strategies to prevent vascular damages, we have developed original mice models of arterial lesions (mechanical injury of carotids, humanized model of aorta transplantation) found in cardiovascular diseases and in transplant vasculopathies. In collaboration with industrial partners and clinicians, we plan to test various chemicals compounds targeting PI3K/mTOR signaling pathways in these pre-clinical models and eventually develop a translational approach towards patients.
SELECTED PUBLICATIONS
Single-cell transcriptome mapping identifies a local, innate B cell population driving chronic rejection after lung transplantation. Smirnova N, Riemondy K, Bueno M, Collins S, Suresh P, Wang X, Patel K.N, Cool C, Königshoff M, Sharma N.S, and Eickelberg O. JCI Insight. 2022. Pubmed
Smooth muscle cells-derived CXCL10 prevents endothelial healing through PI3Kγ-dependent T cells response. . Cardiovasc Res. 2020Pubmed
PI3KC2α-dependent and VPS34-independent generation of PI3P controls primary cilium-mediated autophagy in response to shear stress. Nat Comm. 2020. Pubmed
A non-catalytic function of PI3Kγ drives smooth muscle cell proliferation after arterial damage. J. Cell. Science. 2020.Pubmed
Immune and Smooth Muscle Cells Interactions in Atherosclerosis: How to Target a Breaking Bad Dialogue?


Inserm/UPS UMR 1297 - I2MC Institut des Maladies Métaboliques et Cardiovasculaires
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