Familial Aortopathies and Cellular Exploration

Not Applicable

• Conditions: Familial Aortopathies
• Interventions: Biological: blood sample

• Registration Number: NCT05401500
• Lead Sponsor: Assistance Publique Hopitaux De Marseille

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..

Detailed Description

Not available

Study Timeline

• Status Verified: 2022-05
• Study First Submitted: 2022-05-19
• Study Start: 2022-06-01
• Study First Submitted QC: 2022-06-01
• Last Update Submitted: 2022-06-01
• Study First Posted: 2022-06-02
• Last Update Posted: 2022-06-02
• Primary Completion: 2022-07-01
• Study Completion: 2023-06-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 3

Inclusion Criteria

• patient with a mutation in the ACTA2 gene

Exclusion Criteria

• patient under 18 years of age at the time of inclusion

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
familial aortopathy	blood sample	-

Primary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Assistance Publique Hopitaux de Marseille; 🇫🇷 Marseille, France