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Preau 2014 Thesis University Lille

From Bioblast
Publications in the MiPMap
Preau S (2014) Implication du cytosquelette dans les dysfonctions myocardiques : exemple de la cardiomyopathie septique. Thesis University Lille 155pp.

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Preau S (2014) Thesis University Lille

Abstract: The cytoskeleton is composed of intracellular microfilaments (actin polymers), microtubules (tubulin polymers) and intermediate filaments (desmin, lamin … polymers). Sepsis, the association of infection and systemic inflammatory response, induces myocardial dysfunction. Septic cardiomyopathy appears in the early phase of sepsis and is associated with fatal outcome. Complete recovery of myocardial function occurs within two weeks following the onset of myocardial dysfunction in surviving patients. Although several studies demonstrated a role of cytoskeleton in septic cardiomyopathy, the implication of microfilaments and microtubules is not clear. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine secreted during sepsis that is suggested to postpone myocardium recovery. The first aim of the study was to characterize microtubule implications in MIF-induced cardiac muscle dysfunction. In a model of human right atrial trabecule we demontrated that MIF induces microtubule stabilizations which is responsible for high intracellular viscosity, contractile and mitochondria dysfunctions. Our results suggest that MIF-induced microtubule stabilizations might be responsible for a delay of myocardial recovery during septic cardiomyopathy. The second aim of the study was to characterize microfilament implications in a murine inflammatory cardiomyopathy induced by lipopolysaccharid (LPS) injection. Our results suggest that microfilament stabilizations might be responsible for LPS-induced contractile and mitochondria dysfunction in the early phase of inflammatory cardiomyopathy. Thus, these new fundamental mechanisms suggest direct implication of microtubules and microfilaments in the development and evolution of inflammatory cardiomyopathies.


Labels: MiParea: Respiration  Pathology: Sepsis 

Organism: Mouse  Tissue;cell: Heart  Preparation: Permeabilized tissue 

Regulation: ADP  Coupling state: LEAK, OXPHOS  Pathway: N, S  HRR: Oxygraph-2k