Fibroblasts and Thoracic Aortic Aneurysms: in Vitro Characterization in With Marfan Syndrome and Genetic Aortic Diseases (FIBRA)

FIBROBLASTS AND THORACIC AORTIC ANEURYSMS: IN VITRO CHARACTERIZATION IN PATIENTS WITH MARFAN SYNDROME AND GENETIC AORTIC DISEASES

The aim of the present study is to characterise the phenotype of fibroblasts and to classify different mechanisms involved in the onset and progression of TAAD in syndromic and non-syndromic subjects in order to evaluate potential markers related to TAAD.

Study Overview

• Status: Enrolling by invitation
• Conditions: Marfan Syndrome; Rare Diseases; Thoracic Aortic Aneurysm (TAA)

Detailed Description

The aim of the study is to analyse cutaneous fibroblast properties in patients with thoracic aortic aneurysms (both syndromic and non-syndromic) to identify differences in molecular mechanisms in collagen turnover pathways compared to healthy controls in the general population.

• Study Type: Observational
• Enrollment (Estimated): 15

Contacts and Locations

Study Locations

• Italy
  • Milan
    • San Donato Milanese, Milan, Italy, 20097
      • Cardiovascular Genetic Centre IRCCS Policlinico San Donato

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

resaerch hospital for rare cardiovascular diseases

Description

Inclusion Criteria (general for the study):

signed informed consent; subjects aged 18 years and above.

Inclusion Criteria (Case):

subjects with Marfan syndrome and thoracic aortic aneurysms (in clinical follow-up or with cardiac surgery program); subjects with non-syndromic thoracic aortic aneurysms (in clinical follow-up or with cardiac surgery program);

Inclusion Criteria (healthy controls):

absence of any aortic/thoracic disease;

Exclusion Criteria (all groups):

• Presence of any confounding cardiovascular risk factor (hypertension, dyslipidaemia, diabetes, smoking habits) or previous cardiovascular disease
• Corticosteroid or Steroids or Fluorochinolones treatment within six months before enrollment Subjects on chronic immunosuppressive therapies such as oral steroids, but also on chronic topical steroids in the area of investigation;
• A history of keloid formation (data found in anamnesis and medical records);
• Anaesthetic drug allergy (data found in anamnesis and medical records).

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Syndromic TAA; Presence of thoracic aortic aneurysms and pleiotropic effects
Non-syndromic TAA; Presence of thoracic aortic aneurysms without pleiotropic effects
Healthy Controls; healthy volunteers from the general population, matched fro age with the two case groups

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fibroblasts phenotype: cell morphology and migration	cell morphology: phase-contrast microscopy	12 months
Fibroblasts phenotype: cell morphology and migration	Cell migration: wound healing assay (scratch test).	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expression of genes and proteins involved in collagen turnover and extracellular matrix remodeling pathways	mRNA extraction and real-time PCR to assess the expression of genes involved in collagen turnover;	16 months
Expression of genes and proteins involved in collagen turnover and extracellular matrix remodeling pathways	Slot blot to assess ECM proteins and degrading proteases.	16 months
Levels of metalloproteinases involved in ECM degradation	SDS-zymography	24 months

Collaborators and Investigators

• Sponsor: IRCCS Policlinico S. Donato
• Collaborators: University of Milan

Publications and helpful links

General Publications

• Lu P, Takai K, Weaver VM, Werb Z. Extracellular matrix degradation and remodeling in development and disease. Cold Spring Harb Perspect Biol. 2011 Dec 1;3(12):a005058. doi: 10.1101/cshperspect.a005058.
• Plikus MV, Wang X, Sinha S, Forte E, Thompson SM, Herzog EL, Driskell RR, Rosenthal N, Biernaskie J, Horsley V. Fibroblasts: Origins, definitions, and functions in health and disease. Cell. 2021 Jul 22;184(15):3852-3872. doi: 10.1016/j.cell.2021.06.024.
• Ignotz RA, Massague J. Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J Biol Chem. 1986 Mar 25;261(9):4337-45.

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: January 9, 2025
• First Submitted That Met QC Criteria: January 15, 2025
• First Posted (Actual): January 22, 2025

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Fibroblasts; Collagen turnover; thoracic aortic aneuryms
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Disease Attributes; Genetic Diseases, Inborn; Connective Tissue Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Abnormalities, Multiple; Aortic Diseases; Bone Diseases, Developmental; Aneurysm; Aortic Aneurysm; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Rare Diseases; Aortic Aneurysm, Thoracic; Marfan Syndrome
• Other Study ID Numbers: FIBRA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD sharing will be defined at the active enrolment process of the study

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No