Familial Aortopathies
Conditions
Brief summary
The prevalence of hereditary aortic disease (HTAD), responsible for aneurysm or dissection, is estimated at 25%. Mutations in the ACTA2 gene represent the main cause of non-syndromic forms (10-21%). ACTA2 is expressed in vascular wall smooth muscle cells (VSMC) and encodes alpha actin (α-SMA). This actin isoform is in the majority in VSMCs and plays a key role in their contractile properties. The mutations are dominant-negative and lead, in a fibroblast model, to defects in the organisation of the actin cytoskeleton and to an increase in the migratory and proliferative potential of the cells. In vivo, VSCMs exist in a phenotypic continuum ranging from a quiescent differentiated contractile state to a so-called synthetic state in which cells are proliferative, synthesise extracellular matrix elements and exhibit enhanced migratory capabilities. To understand how ACTA2 mutations deregulate VSMC functions and steer them towards a synthetic phenotype, it is necessary to have a cellular model as close as possible to the affected tissue..
Interventions
BIOLOGICALblood sample
blood sampling
Sponsors
Assistance Publique Hopitaux De Marseille
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* patient with a mutation in the ACTA2 gene
Exclusion criteria
* patient under 18 years of age at the time of inclusion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| analysis of the impact of ACTA2 mutations on the morphology of the actin cytoskeleton | baseline | use of a model of IPS cells reprogrammed into VSMCs from patients with ACTA2 mutations, compared to a healthy control |
Countries
France
Contacts
Primary ContactLaurence Bal, MD
Outcome results
None listed