Clinical trial NCT05434481: MITAORTA - Role of Mitochondrial Dynamic in Aneurysm and Dissection of Ascending Thoracic Aorta
Official title: MITAORTA - Role of Mitochondrial Dynamic in Aneurysm and Dissection of Ascending Thoracic Aorta
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Aortic Aneurysm and Dissection
Keywords: extracellular matrix
cell survival
oxydative stress
mitochondrial fusion
metabolomic profiling of aortic aneurym
metabolomic profilng of aortic dissection
Lead sponsor: University Hospital, Angers
Sponsor class: OTHER_GOV
Collaborators: name: Fondation de l'Avenir
First posted: 2022-06-28
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Aneurysm and Dissection of Ascending Thoracic Aorta
Primary purpose: OTHER

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

Detailed description: In an aortic aneurysm process, the alteration of the extracellular matrix (ECM) as well as the apoptosis of the smooth muscle cells are due to inflammatory phenomena and oxydative stress, involving mitochondria which has a key place within cells.

Mitochondrial fusion and fission constitute mitochondrial dynamic and are involved in the mechanisms described above.

The alteration of mitochondrial dynamics has been demonstrated in many pathologies, in particular neurological, cancer and cardiovascular disease and generally occurs in favor of fission.

In a mouse model (FASEB J, 2021, Robert P ), the role of mitochondrial fusion has been demostrated as a protective factor against hypertension in resistance arteries and a deletion of OPA1 (optic Atrophy 1) fusion protein may lead to aneurysm until aortic dissection. The results of this experimental study suggest a role of the alteration of mitochondrial dynamic in the development of aneurysm and aortic dissection.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Level of tissue expression of the genes and coding for the proteins (Optic Atrophy 1) OPA1
timeFrame: 1 month
measure: Level of tissue expression of the genes and coding for the proteins MFN1 (Mitofusin 1)
timeFrame: 1 month
measure: Level of tissue expression of the genes and coding for the proteins MFN2 (Mitofusin 2)
timeFrame: 1 month
measure: Level of tissue expression of the genes and coding for the proteins Fis1
timeFrame: 1 month
measure: Level of tissue expression of the genes and coding for the proteins Drp1
timeFrame: 1 month
measure: Level of tissue expression of the genes and coding for the proteins Nfr1
timeFrame: 1 month
measure: Level of tissue expression of the genes and coding for the proteins Tfam
timeFrame: 1 month
measure: Level of tissue expression of the genes and coding for the proteins PGC1⍺
timeFrame: 1 month
measure: Analysis of mitochondrial network
timeFrame: 1 month
Secondary outcomes:
measure: Protein of remodelling and constitution of extracellular matrix: Metalloprotease MMp2
timeFrame: 1 month
measure: Proteins of remodelling and constitution of extracellular matrix: Timp 1/2
timeFrame: 1 month
measure: Proteins of remodelling and constitution of extracellular matrix: Collagene I/III
timeFrame: 1 month.
measure: Protein of remodelling and constitution of extracellular matrix: Elastine
timeFrame: 1 month
measure: Proteins of survival cell: Bcl2/Bax
timeFrame: 1 month
measure: Proteins of survival cell: Cytochrome C
timeFrame: 1 month
measure: Proteins of oxydative stress: NADPH
timeFrame: 1 month
measure: Proteins of oxydative stress: OxyD
timeFrame: 1 month
measure: Proteins of oxydative stress: Sod 1/2
timeFrame: 1 month
measure: Proteins of Smooth Muscle Cell reactivity: Myh11
timeFrame: 1 month
measure: Proteins of Smooth Muscle Cell reactivity: Acta 2
timeFrame: 1 month
measure: Proteins of Smooth Muscle Cell reactivity: MLC20
timeFrame: 1 month
measure: Proteins of Smooth Muscle Cell reactivity: Rock1
timeFrame: 1 month
measure: Proteins of Smooth Muscle Cell reactivity: Rhoa
timeFrame: 1 month
measure: Analysis of Plasma Metabolomes
timeFrame: 2 years
measure: Analysis of Aorta Metabolomes
timeFrame: 2 years
Other outcomes:
Locations:
city: Angers
country: France
facility: Olivier FOUQUET
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.