MITAORTA - Role of Mitochondrial Dynamic in Aneurysm and Dissection of Ascending Thoracic Aorta

NCT05434481 | Active Not Recruiting

• 1 other identifier: 2022-A00719-34
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The main objective is to compare the mitochondrial dynamic between patients operated for aneurysm of ascending aorta or type A aortic dissection (AAD) or control group

Conditions

Aortic Aneurysm and Dissection

Keywords

extracellular matrix; cell survival; oxydative stress; mitochondrial fusion; metabolomic profiling of aortic aneurym; metabolomic profilng of aortic dissection

Outcome Measures

Primary Outcomes (9)

• Level of tissue expression of the genes and coding for the proteins (Optic Atrophy 1) OPA1

  Level expression of, (Optic Atrophy 1) OPA1 by RT-qPCR

  1 month

• Level of tissue expression of the genes and coding for the proteins MFN1 (Mitofusin 1)

  Level expression of MFN1 (Mitofusin 1) by RT-qPCR

  1 month

• Level of tissue expression of the genes and coding for the proteins MFN2 (Mitofusin 2)

  Level expression of MFN2 (Mitofusin 2) by RT-qPCR

  1 month

• Level of tissue expression of the genes and coding for the proteins Fis1

  Level expression of Fis1 by RT-qPCR

  1 month

• Level of tissue expression of the genes and coding for the proteins Drp1

  Level expression of Drp1 by RT-qPCR

  1 month

• Level of tissue expression of the genes and coding for the proteins Nfr1

  Level expression of Nfr1 by RT-qPCR

  1 month

• Level of tissue expression of the genes and coding for the proteins Tfam

  Level expression of Tfam by RT-qPCR

  1 month

• Level of tissue expression of the genes and coding for the proteins PGC1⍺

  Level expression of PGC1⍺ by RT-qPCR

  1 month

• Analysis of mitochondrial network

  To analyze the mitochondrial network, vascular smooth muscle cells will be extracted from the wall of aorta samples and seeded in Petri dish. When 80% confluence is obtained, cells will be incubated with a green fluorescent marker (Mitotacker Green Probes) and 3D fluorescence microscopy will be used. Analysis of mitochondrial network will be done after characterization of mitochondrial shapes and distribution in the different aorta samples.

  1 month

Secondary Outcomes (16)

• Protein of remodelling and constitution of extracellular matrix: Metalloprotease MMp2

  1 month

• Proteins of remodelling and constitution of extracellular matrix: Timp 1/2

  1 month

• Proteins of remodelling and constitution of extracellular matrix: Collagene I/III

  1 month.

• Protein of remodelling and constitution of extracellular matrix: Elastine

  1 month

• Proteins of survival cell: Bcl2/Bax

  1 month

Study Arms (3)

Aneurysm group

ACTIVE COMPARATOR

Patients operated for aneurysm of the ascending aorta according the guidelines on the diagnosis and treatment of aortic diseases (European Society of Cardiology - 2014).

Other: Mitochondrial dynamic analysis in the aorta samples and metabolomic profiling in the aortic diseases

Type A aortic dissection group

ACTIVE COMPARATOR

Patients operated for type A aortic dissection according the guidelines on the diagnosis and treatment of aortic diseases (European Society of Cardiology - 2014).

Other: Mitochondrial dynamic analysis in the aorta samples and metabolomic profiling in the aortic diseases

Control group

SHAM COMPARATOR

Patients without aortic aneurysm or aortic dissection operated for aortic valve replacement (AVR) and/or coronary artery bypass with a saphenous vein graft for proximal aortic anastomosis to collect the aortic sample. For patients operated for AVR, an aortic sample will be collected before closing the aorta.

Other: Mitochondrial dynamic analysis in the aorta samples and metabolomic profiling in the aortic diseases

Interventions

Mitochondrial dynamic analysis in the aorta samples and metabolomic profiling in the aortic diseases OTHER

* For each patient: a segment of aorta will be sampled and cutted into 4 parts * 1 fragment placed in a Falcon tube containing DMEM (Dulbecco's Modified Eagle Medium, Thermo Fisher®), temporarily stored at + 4°C, for primary culture of smooth muscle cells will allow analysis of the mitochondrial network. * 1 fragment placed in a Falcon tube containing Allprotect Tissue Reagent (QIAGEN®), stored at -80°C for gene (RT-PCR) and protein (Western Blot) analysis. * 2 fragments each placed in dry cryotube stored at - 80°C will be used for metabolomic analysis. * For each patient, 2 arterial blood samples will be collected before general anaesthesia * One tube of whole blood stored at -80°C for metabolomic analysis. * One tube of blood stored at -80°C for plasma cytokines

Aneurysm group; Control group; Type A aortic dissection group

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aneurysm aortic group: patients treated for an aneurysm of the ascending thoracic aorta with surgical indication according to the ESC guidelines (2014).
• Aortic dissection group: patients treated for type A acute aortic dissection or intramural hematoma of the ascending thoracic aorta in emergency.
• Control group: patients operated for aortic valve replacement (little aortic sample before closing aortotomy) or coronary artery bypass grafting which the use of a saphenous graft and the performance of a proximal anastomosis on the ascending aorta is planned

You may not qualify if:

• Patients under 18 years old
• Other acute aortic syndromes (penetrating ulcers, iatrogenic or traumatic dissections)
• Patients treated for aortic valve replacement in the context of infective endocarditis
• Patients treated for emergency aortic valve replacement or coronary bypass surgery\*\*
• Pregnant, parturient and breastfeeding women
• Patients protected by an administrative or judicial measure (curatorship, guardianship)
• Patients receiving psychiatric care under duress
• Adults subject to a legal protection measure.
• Patients whose the samples planned for the study could not be taken;
• Patients in the control group whose tissue sampling will not be performed.

Sponsors & Collaborators

• University Hospital, Angers: lead
• Fondation de l'Avenir: collaborator

Study Sites (1)

Olivier FOUQUET

Angers, France

Location

Related Publications (6)

• Trabado S, Al-Salameh A, Croixmarie V, Masson P, Corruble E, Feve B, Colle R, Ripoll L, Walther B, Boursier-Neyret C, Werner E, Becquemont L, Chanson P. The human plasma-metabolome: Reference values in 800 French healthy volunteers; impact of cholesterol, gender and age. PLoS One. 2017 Mar 9;12(3):e0173615. doi: 10.1371/journal.pone.0173615. eCollection 2017.

  PMID: 28278231 BACKGROUND

• Robert P, Nguyen PMC, Richard A, Grenier C, Chevrollier A, Munier M, Grimaud L, Proux C, Champin T, Lelievre E, Sarzi E, Vessieres E, Henni S, Prunier D, Reynier P, Lenaers G, Fassot C, Henrion D, Loufrani L. Protective role of the mitochondrial fusion protein OPA1 in hypertension. FASEB J. 2021 Jul;35(7):e21678. doi: 10.1096/fj.202000238RRR.

  PMID: 34133045 RESULT

• Toda M, Yamamoto K, Shimizu N, Obi S, Kumagaya S, Igarashi T, Kamiya A, Ando J. Differential gene responses in endothelial cells exposed to a combination of shear stress and cyclic stretch. J Biotechnol. 2008 Jan 20;133(2):239-44. doi: 10.1016/j.jbiotec.2007.08.009. Epub 2007 Aug 9.

  PMID: 17850909 RESULT

• Archer SL. Mitochondrial dynamics--mitochondrial fission and fusion in human diseases. N Engl J Med. 2013 Dec 5;369(23):2236-51. doi: 10.1056/NEJMra1215233. No abstract available.

  PMID: 24304053 RESULT

• Piquereau J, Caffin F, Novotova M, Prola A, Garnier A, Mateo P, Fortin D, Huynh le H, Nicolas V, Alavi MV, Brenner C, Ventura-Clapier R, Veksler V, Joubert F. Down-regulation of OPA1 alters mouse mitochondrial morphology, PTP function, and cardiac adaptation to pressure overload. Cardiovasc Res. 2012 Jun 1;94(3):408-17. doi: 10.1093/cvr/cvs117. Epub 2012 Mar 8.

  PMID: 22406748 RESULT

• Le Page S, Niro M, Fauconnier J, Cellier L, Tamareille S, Gharib A, Chevrollier A, Loufrani L, Grenier C, Kamel R, Sarzi E, Lacampagne A, Ovize M, Henrion D, Reynier P, Lenaers G, Mirebeau-Prunier D, Prunier F. Increase in Cardiac Ischemia-Reperfusion Injuries in Opa1+/- Mouse Model. PLoS One. 2016 Oct 10;11(10):e0164066. doi: 10.1371/journal.pone.0164066. eCollection 2016.

  PMID: 27723783 RESULT

MeSH Terms

Conditions

Aortic Dissection

Condition Hierarchy (Ancestors)

Dissection, Blood Vessel; Aneurysm; Vascular Diseases; Cardiovascular Diseases; Acute Aortic Syndrome; Aortic Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Aneurysm and Dissection of Ascending Thoracic Aorta

Study Record Dates

• First Submitted: June 3, 2022
• First Posted: June 28, 2022
• Study Start: September 7, 2022
• Primary Completion: October 23, 2023
• Study Completion: October 23, 2024
• Last Updated: June 11, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)