Controle du Phenotype des Cellules Musculaires Lisses
Responsable Isabelle LIMON
The team’s main goal is to identify mechanisms and entities which regulate adult vessel wall smooth muscle cell (VSMC) phenotype change, a process contributing to the pathogenesis of numerous cardiovascular disorders. Phenotypic changes in VSMC biology, in the context of arterial tissue-specific spatio-temporal physiology and structure, are important determinants of the evolution of atherothrombotic and non-atherothrombotic pathologies within the arterial wall. Atherosclerosis is the cause of most heart attacks and strokes, and is undoubtedly, an age-related disease. There is growing evidence for a pivotal role of VSMC phenotypic switching in atherosclerosis. Because we have demonstrated that Adenylyl Cyclase (AC) 8 expression is closely linked to the properties developed by VSMC in atherosclerosis and hyperplasia post-angioplasty, one of our 2 projects aims in characterizing the functional role of AC8 in pathological vascular remodelling as well as the impact of aging on AC8-regulated VSMC function; it will also specify the AC8-induced signaling pathways involved in trans-differentiated VSMC responses including the effect of AC8 over-expression on cAMP/EPAC signal integration using FRET biosensors imaging. Taking advantage of our background, we expanded our projects and started deciphering mechanisms which possibly disrupt cerebro-vascular integrity in the aged brain. Such disruption to cerebro-vascular integrity is a major risk factor for Alzheimer's disease and vascular dementia. Regarding the importance of inflammation in vascular alterations, we will further investigate cell type specific contribution to- and the molecular mechanisms underlying- the inflammatory context generated by ?-amyloid accumulation in vessel walls. We plan to establish miRNA profiling of ?-amyloid-treated endothelial and smooth muscle cells for a better understanding of the early events of the disease progression. We should also characterize in vivo the potential beneficial effect of the truncated form of thioredoxin, Trx-80, on the ontogenesis of cerebrovascular amyloid angiopathy and Alzheimer disease. The rationale for such a project relies on several observations demonstrating that Trx-80 inhibits amyloid-? aggregation. These studies bring the Unit’s investigation to the interface between fundamental molecular biology, neuroscience and cardiovascular pathophysiology and the effect of age thereon.

B2A UMR 8256 @Février 2014